Ignite Creation Date:
2025-12-25 @ 4:34 AM
Ignite Modification Date:
2026-03-06 @ 12:01 PM
Study NCT ID:
NCT02517918
Status:
COMPLETED
Last Update Posted:
2025-06-08
First Post:
2015-02-19
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Metronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012516', 'term': 'Osteosarcoma'}], 'ancestors': [{'id': 'D018213', 'term': 'Neoplasms, Bone Tissue'}, {'id': 'D009372', 'term': 'Neoplasms, Connective Tissue'}, {'id': 'D018204', 'term': 'Neoplasms, Connective and Soft Tissue'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D012509', 'term': 'Sarcoma'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D008727', 'term': 'Methotrexate'}, {'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D000077211', 'term': 'Zoledronic Acid'}], 'ancestors': [{'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D000630', 'term': 'Aminopterin'}, {'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D004164', 'term': 'Diphosphonates'}, {'id': 'D063065', 'term': 'Organophosphonates'}, {'id': 'D007093', 'term': 'Imidazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'S.Mathoulin@bordeaux.unicancer.fr', 'phone': '0556333333', 'title': 'Pr Simone Mathoulin-Pelissier', 'organization': 'Institut Bergonié'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': "Safety profile was continuously followed : monitored every 28 days during treatment consultation and up to 30 days after the last treatment administration or until the start of a new antitumor therapy, whichever occurs first. In case of SAE, monitoring could be improved as per investigator's judgement. After treatment discontinuation, patients were followed up 4 weeks later for toxicities. Grade 3 or 4 toxicity were monitored until resolution, through study completion, an average of 13 months.", 'description': 'Safety population: all patients having received at least one treatment administration.\n\nAll adverse events (related and unrelated to treatment) are reported. All serious adverse events (related and unrelated to treatment) are reported.\n\nAdverse events will be graded using the NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE).', 'eventGroups': [{'id': 'EG000', 'title': 'Dose Escalation Part With Sirolimus (Si) Dose 4 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 6. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.', 'otherNumAtRisk': 6, 'otherNumAffected': 6, 'seriousNumAtRisk': 6, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Dose Escalation Part With Sirolimus (SI) Dose 6 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 6 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 3. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.', 'otherNumAtRisk': 3, 'otherNumAffected': 3, 'seriousNumAtRisk': 3, 'seriousNumAffected': 3}, {'id': 'EG002', 'title': 'Expansion Cohort With Dose Sirolimus (SI) 4 mg', 'description': 'Prospective open-labeled phase I trial. The expansion cohort is designed to enable to detect antitumor activity observed with sirolimus (SI) combined with cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA).\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 14. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.', 'otherNumAtRisk': 14, 'otherNumAffected': 14, 'seriousNumAtRisk': 14, 'seriousNumAffected': 9}], 'otherEvents': [{'term': 'Anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 6, 'numAffected': 4}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Sinus tachycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Glaucoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Cheilitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Dry mouth', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Gastritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Gastroesophageal reflux disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Gastrointestinal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hemorrhoids', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Mucositis oral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 5, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 8, 'numAffected': 6}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Edema face', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Fever', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Flu like symptoms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Non-cardiac chest pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Bronchial infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Gum infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Nail infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Skin infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 5, 'numAffected': 5}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Alkaline phosphatase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Blood bilirubin increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'CPK increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Cholesterol high', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'GGT increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Lymphocyte count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 6, 'numAffected': 6}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Lymphocyte count increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Neutrophil count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Platelet count decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 8, 'numAffected': 7}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Weight loss', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Anorexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hyperglycemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypoalbuminemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypocalcemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypoglycemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypokalemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypomagnesemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypophosphatemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, 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'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Erythema multiforme', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Nail loss', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Rash maculo-papular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Skin hypopigmentation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Skin ulceration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Superior vena cava syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'WORSENING OF GENERAL STATUS', 'notes': 'General disorders and administration site conditions - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'INFLAMMATORY SYNDROM', 'notes': 'General disorders and administration site conditions - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'HOT FLUSHES', 'notes': 'General disorders and administration site conditions - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'POLYDYPSIA', 'notes': 'General disorders and administration site conditions - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'ALTERATION OF GENERAL STATUS', 'notes': 'General disorders and administration site conditions - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'LDH INCREASED', 'notes': 'Investigations - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'CRP INCREASED', 'notes': 'Investigations - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'IRON DEFICIENCY', 'notes': 'Metabolism and nutrition disorders - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'SUBCUTANEOUS NODULE', 'notes': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'DYSURIA', 'notes': 'Renal and urinary disorders - Other, specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Renal and urinary 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specify', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}], 'seriousEvents': [{'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Musculoskeletal chest pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Interstitial lung disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Ascites', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 7, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'General 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'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 5, 'numAffected': 3}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Respiratory distress', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Diverticulitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Pleural effusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Fever', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypokalaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Pulmonary embolism', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}, {'term': 'Hypophosphataemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 14, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'Version 4.0 (CTCAE)'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Dose Escalation Part: Number of Dose-Limiting Toxicities (DLTs) at Each Dose Level on Cycle 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Dose Escalation Part With Sirolimus (Si) Dose 4 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 6. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'OG001', 'title': 'Dose Escalation Part With Sirolimus (SI) Dose 6 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 6 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 3. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'During the first cycle (28 days)', 'description': 'A DLT is defined as an adverse event (AE) or laboratory abnormality that fulfills the criteria below:\n\n* Is considered to be at least possibly related to the study treatment\n* Occurs during the first cycle of treatment\n* Is unrelated to disease, disease progression, inter-current illness, or concomitant medications\n* Meets one of the criteria below, graded as outlined or according to NCI CTCAEv4.3:\n\n * Grade 4 non-haematological toxicity (not laboratory)\n * Grade 3 non-haematological toxicity \\> 3 days (not laboratory) (except for asthenia, 1rst episode of nausea/vomiting without maximal symptomatic/prophylactic treatment)\n * Grade ≥ 3 non-hematologic laboratory value if medical intervention is required to treat the patient, or the abnormality leads to hospitalization, or the abnormality persists for \\> 1 week\n * Grade ≥ 3 hematologic toxicity \\> 3 days (except for lymphopenia)\n * Grade 4 lymphopenia\n * Confirmed febrile neutropenia', 'unitOfMeasure': 'Number of DLTs', 'reportingStatus': 'POSTED', 'populationDescription': "Population assessable : Patients who received at least one dose of one of the trial's products and have received the complete C1 cycle (28 days: D1 to D28) or have exhibited a DLT during C1."}, {'type': 'PRIMARY', 'title': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, in Terms of 6-month Non-progression Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Expansion Cohort With Dose Sirolimus (SI) 4 mg', 'description': 'Prospective open-labeled phase I trial. The expansion cohort is designed to enable to detect antitumor activity observed with sirolimus (SI) combined with cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA).\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 14. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'title': 'Complete response', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Partial response confirmed', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Stable disease', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Progression', 'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}]}]}, {'title': 'Unevaluable according to RECIST v1.1', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6-month non-progression rate as per RECIST v1.1', 'description': '6-month non-progression rate defined as the rate of complete or partial response or stable disease at 6 months using RECIST v1.1 :\n\n* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\<10 mm.\n* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.\n* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).\n* Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD\n* Unevaluable : patients stopped the treatment before tumor assessment.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Population assessable : Patients eligible and who received at least one complete or two incomplete treatment cycles and least one disease measurement recorded not less than eight weeks after treatment onset.'}, {'type': 'SECONDARY', 'title': 'Dose Escalation Part : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, Best Objective Response Rate (ORR) as Per RECIST v1.1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Dose Escalation Part With Sirolimus (Si) Dose 4 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 6. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'OG001', 'title': 'Dose Escalation Part With Sirolimus (SI) Dose 6 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 6 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 3. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'title': 'Completed response', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Partial response', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'Stable disease', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Progression', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'Inevaluable for response', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 4 months.', 'description': 'The best objective response (BOR) is the best response recorded for each patient from the start of the study treatment until the end of treatment for progressive disease, death, patient or investigator decision.\n\nBOR is determined by investigator review of tumor assessments using RECIST v1.1 :\n\n* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\<10 mm\n* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters\n* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm\n* Stable Disease (SD)\n\nTumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, average of 4 months', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': "Population assessable : Patients who received at least one dose of one of the trial's products and have received the complete C1 cycle (28 days: D1 to D28) or have exhibited a DLT during C1."}, {'type': 'SECONDARY', 'title': 'Dose Escalation Part : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Progression-free Survival (PFS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Dose Escalation Part With Sirolimus (Si) Dose 4 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 6. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'OG001', 'title': 'Dose Escalation Part With Sirolimus (SI) Dose 6 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 6 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 3. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '1-year Progression-free survival (PFS) as per RECIST v1.1', 'description': '1-year Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).\n\nProgressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': "Population assessable : Patients who received at least one dose of one of the trial's products and have received the complete C1 cycle (28 days: D1 to D28) or have exhibited a DLT during C1."}, {'type': 'SECONDARY', 'title': 'Dose Escalation Part : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Overall Survival (OS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Dose Escalation Part With Sirolimus (Si) Dose 4 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 6. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'OG001', 'title': 'Dose Escalation Part With Sirolimus (SI) Dose 6 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 6 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 3. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '1-year Overall Survival (OS) as per RECIST v1.1', 'description': '1-year Overall Survival (OS) is defined as the time from first infusion to death (of any cause)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': "Population assessable : Patients who received at least one dose of one of the trial's products and have received the complete C1 cycle (28 days: D1 to D28) or have exhibited a DLT during C1."}, {'type': 'SECONDARY', 'title': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, Best Objective Response Rate (ORR) as Per RECIST v1.1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Expansion Cohort With Dose Sirolimus (SI) 4 mg', 'description': 'Prospective open-labeled phase I trial. The expansion cohort is designed to enable to detect antitumor activity observed with sirolimus (SI) combined with cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA).\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 14. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'title': 'Complete response', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Confirmed Partial response', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Stable disease', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}, {'title': 'Progression', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}]}]}, {'title': 'Inevaluable for response', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 4 months.', 'description': 'The best objective response (BOR) is the best response recorded for each patient from the start of the study treatment until the end of treatment for progressive disease, death, patient or investigator decision.\n\nBOR is determined by investigator review of tumor assessments using RECIST v1.1 :\n\n* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\<10 mm\n* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters\n* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm\n* Stable Disease (SD) Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 4 months', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Population assessable : Patients eligible and who received at least one complete or two incomplete treatment cycles and least one disease measurement recorded not less than eight weeks after treatment onset.'}, {'type': 'SECONDARY', 'title': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Progression-free Survival (PFS) as Per RECIST v1.1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Expansion Cohort With Dose Sirolimus (SI) 4 mg', 'description': 'Prospective open-labeled phase I trial. The expansion cohort is designed to enable to detect antitumor activity observed with sirolimus (SI) combined with cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA).\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 14. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.8', 'groupId': 'OG000', 'lowerLimit': '1.4', 'upperLimit': '3.6'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '1-year Progression-free survival (PFS) as per RECIST v1.1', 'description': '1-year Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).\n\nProgressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Population assessable : Patients eligible and who received at least one complete or two incomplete treatment cycles and least one disease measurement recorded not less than eight weeks after treatment onset.'}, {'type': 'SECONDARY', 'title': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Overall Survival (OS) as Per RECIST v1.1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '14', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Expansion Cohort With Dose Sirolimus (SI) 4 mg', 'description': 'Prospective open-labeled phase I trial. The expansion cohort is designed to enable to detect antitumor activity observed with sirolimus (SI) combined with cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA).\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 14. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'classes': [{'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '1-year Overall Survival (OS) as per RECIST v1.1', 'description': '1-year Overall Survival (OS) is defined as the time from first infusion to death (of any cause)', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Population assessable : Patients eligible and who received at least one complete or two incomplete treatment cycles and least one disease measurement recorded not less than eight weeks after treatment onset.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Dose Escalation Part With Sirolimus (Si) Dose 4 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 6. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'FG001', 'title': 'Dose Escalation Part With Sirolimus (SI) Dose 6 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 6 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 3. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'FG002', 'title': 'Expansion Cohort With Dose Sirolimus (SI) 4 mg', 'description': 'Prospective open-labeled phase I trial. The expansion cohort is designed to enable to detect antitumor activity observed with sirolimus (SI) combined with cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA).\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 14. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '3'}, {'groupId': 'FG002', 'numSubjects': '14'}]}, {'type': 'COMPLETED', 'comment': "Population assessable :\n\nDose escalation part (tolerance) : Patients who received at least one dose of one of the trial's products and have received the complete C1 cycle (28 days: D1 to D28) or have exhibited a DLT during C1.\n\nExpansion cohort (efficacy) : Patients eligible and who received at least one complete or two incomplete treatment cycles and least one disease measurement recorded not less than eight weeks after treatment onset.", 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '3'}, {'groupId': 'FG002', 'numSubjects': '14'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'First patient enrolled: February 16th, 2015 and last patient enrolled: March 11th, 2021'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '14', 'groupId': 'BG002'}, {'value': '23', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Dose Escalation Part With Sirolimus (Si) Dose 4 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 6. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'BG001', 'title': 'Dose Escalation Part With Sirolimus (SI) Dose 6 mg', 'description': 'Prospective open-labeled phase I trial. The dose escalation design to identify the maximum tolerated dose will be the traditional 3+3 design.\n\nSirolimus (SI) dose 6 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 3. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'BG002', 'title': 'Expansion Cohort With Dose Sirolimus (SI) 4 mg', 'description': 'Prospective open-labeled phase I trial. The expansion cohort is designed to enable to detect antitumor activity observed with sirolimus (SI) combined with cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA).\n\nSirolimus (SI) dose 4 mg when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) Sirolimus will be administered per os once daily, continuously. One cycle consits of 28 days.\n\nNumber of subjects : 14. Cyclophosphamide will be administered per os bi-daily (50 mg x 2), and given on a week on/week off schedule.\n\nMethotrexate will be administered per os bi-daily (2.5 mg x 2), and given on day 1 and 4 every week.\n\nZoledronic acid will be administered at home by intravenous infusion (4 mg) on Day 2 of each cycle, every 4 weeks.'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '52.5', 'spread': '13.1', 'groupId': 'BG000'}, {'value': '65.4', 'spread': '12', 'groupId': 'BG001'}, {'value': '36.3', 'spread': '21.4', 'groupId': 'BG002'}, {'value': '44.3', 'spread': '21.0', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}, {'value': '12', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}, {'value': '11', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'France', 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '14', 'groupId': 'BG002'}, {'value': '23', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'All patients included, regardless of whether or not treatment was administered, and regardless violations of any eligibility criteria.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2021-11-09', 'size': 838338, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_000.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2023-04-13T10:21', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'This is a prospective open-labeled phase I trial based on :\n\n* a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA)\n* an expansion cohort once the MTD is established.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 23}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2021-11-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-06-05', 'studyFirstSubmitDate': '2015-02-19', 'resultsFirstSubmitDate': '2023-04-14', 'studyFirstSubmitQcDate': '2015-08-04', 'lastUpdatePostDateStruct': {'date': '2025-06-08', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-06-05', 'studyFirstPostDateStruct': {'date': '2015-08-07', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2025-06-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-09-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Dose Escalation Part: Number of Dose-Limiting Toxicities (DLTs) at Each Dose Level on Cycle 1', 'timeFrame': 'During the first cycle (28 days)', 'description': 'A DLT is defined as an adverse event (AE) or laboratory abnormality that fulfills the criteria below:\n\n* Is considered to be at least possibly related to the study treatment\n* Occurs during the first cycle of treatment\n* Is unrelated to disease, disease progression, inter-current illness, or concomitant medications\n* Meets one of the criteria below, graded as outlined or according to NCI CTCAEv4.3:\n\n * Grade 4 non-haematological toxicity (not laboratory)\n * Grade 3 non-haematological toxicity \\> 3 days (not laboratory) (except for asthenia, 1rst episode of nausea/vomiting without maximal symptomatic/prophylactic treatment)\n * Grade ≥ 3 non-hematologic laboratory value if medical intervention is required to treat the patient, or the abnormality leads to hospitalization, or the abnormality persists for \\> 1 week\n * Grade ≥ 3 hematologic toxicity \\> 3 days (except for lymphopenia)\n * Grade 4 lymphopenia\n * Confirmed febrile neutropenia'}, {'measure': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, in Terms of 6-month Non-progression Rate', 'timeFrame': '6-month non-progression rate as per RECIST v1.1', 'description': '6-month non-progression rate defined as the rate of complete or partial response or stable disease at 6 months using RECIST v1.1 :\n\n* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\<10 mm.\n* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.\n* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).\n* Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD\n* Unevaluable : patients stopped the treatment before tumor assessment.'}], 'secondaryOutcomes': [{'measure': 'Dose Escalation Part : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, Best Objective Response Rate (ORR) as Per RECIST v1.1', 'timeFrame': 'Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 4 months.', 'description': 'The best objective response (BOR) is the best response recorded for each patient from the start of the study treatment until the end of treatment for progressive disease, death, patient or investigator decision.\n\nBOR is determined by investigator review of tumor assessments using RECIST v1.1 :\n\n* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\<10 mm\n* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters\n* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm\n* Stable Disease (SD)\n\nTumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, average of 4 months'}, {'measure': 'Dose Escalation Part : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Progression-free Survival (PFS)', 'timeFrame': '1-year Progression-free survival (PFS) as per RECIST v1.1', 'description': '1-year Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).\n\nProgressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).'}, {'measure': 'Dose Escalation Part : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Overall Survival (OS)', 'timeFrame': '1-year Overall Survival (OS) as per RECIST v1.1', 'description': '1-year Overall Survival (OS) is defined as the time from first infusion to death (of any cause)'}, {'measure': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, Best Objective Response Rate (ORR) as Per RECIST v1.1', 'timeFrame': 'Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from the start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 4 months.', 'description': 'The best objective response (BOR) is the best response recorded for each patient from the start of the study treatment until the end of treatment for progressive disease, death, patient or investigator decision.\n\nBOR is determined by investigator review of tumor assessments using RECIST v1.1 :\n\n* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\<10 mm\n* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters\n* Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions and also demonstrate an absolute increase of at least 5 mm\n* Stable Disease (SD) Tumor assessment were repeated every 8 weeks (±7 days, i.e Week 8, 16, 24, etc.) from start of treatment and at least 4 weeks after the first CR or PR, even if there are treatment delays, an average of 4 months'}, {'measure': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Progression-free Survival (PFS) as Per RECIST v1.1', 'timeFrame': '1-year Progression-free survival (PFS) as per RECIST v1.1', 'description': '1-year Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST v1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).\n\nProgressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).'}, {'measure': 'Expansion Cohort : Antitumor Activity Observed With Sirolimus Combined With CP, MT and ZA, 1-year Overall Survival (OS) as Per RECIST v1.1', 'timeFrame': '1-year Overall Survival (OS) as per RECIST v1.1', 'description': '1-year Overall Survival (OS) is defined as the time from first infusion to death (of any cause)'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Advanced solid tumor', 'Bone metastasis and advanced pretreated osteosarcoma', 'Phase I trial', 'Dose escalation and expansion cohort', 'Biomarkers study'], 'conditions': ['Solid Tumor', 'Osteosarcoma']}, 'referencesModule': {'references': [{'pmid': '31401903', 'type': 'DERIVED', 'citation': 'Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.'}]}, 'descriptionModule': {'briefSummary': 'This is a prospective open-labeled phase I trial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the Maximum Tolerated Dose (MTD) is established.', 'detailedDescription': 'The dose escalation part of the trial will be concerned on adults with advanced solid tumor with bone metastasis and young and adult patients with unresectable locally advanced or metastatic osteosarcoma.\n\nThe Expansion cohort will be conducted on young and adult patients with unresectable locally advanced or metastatic osteosarcoma.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '13 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Histology:\n\n * Advanced solid tumor with radiologically proven bone metastasis, (dose escalation part)\n * Patients with osteogenic osteosarcoma (dose escalation part and expansion cohort) histologically confirmed by central review\n2. Metastatic or unresectable locally advanced disease, not eligible for alternative local treatment (radiotherapy for instance)\n3. Age \\> 18 years for patients with solid tumor and ≥ 13 years for patients with osteosarcoma\n4. ECOG, performance status ≤ 1\n5. Life expectancy \\> 3 months\n6. Measurable disease according to RECIST v1.1. At least one site of disease must be uni-dimensionally ≥ 10 mm\n7. Patients must have histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors, which are not amenable to standard treatment, including for patients with osteosarcoma conventional agents such as anthracyclines, platinum salts, ifosfamide and/or methotrexate\n8. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy\n9. Adequate haematological, renal, metabolic and hepatic function:\n\n * Haemoglobin ≥ 10 g/dl (patients may have received prior red blood cell transfusion, if clinically indicated); leucocytes ≥ 3 x 10\\^9/l, absolute neutrophil count ≥ 1.5 x 10\\^9/l, and platelet count ≥ 120 x 10\\^9/l.\n * Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x upper limit of normality (ULN)\n * Total bilirubin ≤ 1.5 x ULN\n * Calculated creatinine clearance \\> 40 ml/min/1.73 m² (according to MDRD formula)\n * Creatine phosphokinase ≤ 2.5 x ULN\n * Albumin \\> 25 g/l\n10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,\n11. Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the NCI-CTCAE, version 4\n12. Patients with a French social security in compliance with the French law relating to biomedical research\n13. Voluntarily signed and dated written informed consent prior to any study specific procedure\n14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment\n\nExclusion Criteria:\n\n1. Previous treatment with sirolimus\n2. Concomitant diseases/conditions:\n\n * Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions\n * Unstable cardiac disease, pulse oximetry saturation \\< 90% at rest\n * Clinically significant immunodeficiency, such as HIV or active Hepatitis B or C\n * History of auto-immune disease, transplantation\n3. Central nervous system malignancy\n4. Men or women of childbearing potential who are not using an effective method of contraception; women who are pregnant or breast feeding\n5. Patients receiving any substances that are inhibitors or inducers of CYP450 3A4\n6. Ongoing or recent (\\<6 weeks) dental problem, including any severe tooth or jaw infection (mandible and maxilla), dental trauma, dental or stomatological surgery (implants). Current dental cares are allowed\n7. History of maxillary osteonecrosis or delayed healing after dental surgery\n8. Participation to a study involving a medical or therapeutic intervention in the last 30 days\n9. Previous enrolment in the present study\n10. Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons\n11. Known hypersensitivity to any involved study drug or any of its formulation components\n12. Patients receiving live vaccines within 30 days prior to the first dose of study therapy and while participating in study'}, 'identificationModule': {'nctId': 'NCT02517918', 'acronym': 'METZOLIMOS', 'briefTitle': 'Metronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma', 'organization': {'class': 'OTHER', 'fullName': 'Institut Bergonié'}, 'officialTitle': 'Metronomic Cyclophosphamide and Methotrexate Combined With Zoledronic Acid and Sirolimus in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma. A Phase Ib Study From the French Sarcoma Group', 'orgStudyIdInfo': {'id': 'IB 2014-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sirolimus combined with CP, MT and ZA', 'description': 'Drug : Metronomic Cyclophosphamide, Methotrexate, Sirolimus, Zoledronic acid Assessment of the maximum tolerated dose of sirolimus Cyclophosphamide, Methotrexate and Sirolimus will be administrated orally. Zoledronic Acid will be administrated by infusion (IV).', 'interventionNames': ['Drug: Sirolimus combined with CP, MT and ZA']}], 'interventions': [{'name': 'Sirolimus combined with CP, MT and ZA', 'type': 'DRUG', 'otherNames': ['Endoxan, Methotrexate, Rapamune, Zoledronic acid'], 'description': 'Cyclophosphamide, Methotrexate and Sirolimus will be administrated orally. Zoledronic Acid will be administrated by infusion (IV).\n\nTrial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the MTD is established.', 'armGroupLabels': ['Sirolimus combined with CP, MT and ZA']}]}, 'contactsLocationsModule': {'locations': [{'zip': '33076', 'city': 'Bordeaux', 'country': 'France', 'facility': 'Institut Bergonié', 'geoPoint': {'lat': 44.84124, 'lon': -0.58046}}, {'zip': '59000', 'city': 'Lille', 'country': 'France', 'facility': 'Centre Oscar Lambret', 'geoPoint': {'lat': 50.63391, 'lon': 3.05512}}, {'zip': '69008', 'city': 'Lyon', 'country': 'France', 'facility': 'Centre Léon Bérard', 'geoPoint': {'lat': 45.74906, 'lon': 4.84789}}], 'overallOfficials': [{'name': 'Maud TOULMONDE, Doctor', 'role': 'STUDY_CHAIR', 'affiliation': 'Institut Bergonié'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Institut Bergonié', 'class': 'OTHER'}, 'collaborators': [{'name': 'Reliable Cancer Therapies', 'class': 'INDUSTRY'}, {'name': 'Pfizer', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}