Ignite Creation Date:
2025-12-24 @ 6:26 PM
Ignite Modification Date:
2026-04-11 @ 3:01 AM
Study NCT ID:
NCT00036868
Status:
COMPLETED
Last Update Posted:
2024-03-08
First Post:
2002-05-13
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Serbia and Montenegro']}, 'conditionBrowseModule': {'meshes': [{'id': 'D001943', 'term': 'Breast Neoplasms'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D001941', 'term': 'Breast Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068878', 'term': 'Trastuzumab'}, {'id': 'C034456', 'term': 'CMF regimen'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D005472', 'term': 'Fluorouracil'}, {'id': 'D008727', 'term': 'Methotrexate'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'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': 'D014498', 'term': 'Uracil'}, {'id': 'D011744', 'term': 'Pyrimidinones'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic 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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 90}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2002-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-03', 'completionDateStruct': {'date': '2010-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-03-07', 'studyFirstSubmitDate': '2002-05-13', 'studyFirstSubmitQcDate': '2003-01-26', 'lastUpdatePostDateStruct': {'date': '2024-03-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2003-01-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2009-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical heart failure rate measured by New York Heart Association classification, LVEF, and ECG', 'timeFrame': 'from registration'}, {'measure': 'Response rate by RECIST', 'timeFrame': 'from registration'}], 'secondaryOutcomes': [{'measure': 'Duration of response by RECIST', 'timeFrame': 'from registration'}, {'measure': 'Time to progression', 'timeFrame': 'from registration'}, {'measure': 'Toxicity measured by CTC v2.0', 'timeFrame': 'from registration'}]}, 'conditionsModule': {'keywords': ['stage IV breast cancer', 'recurrent breast cancer'], 'conditions': ['Breast Cancer']}, 'referencesModule': {'references': [{'type': 'RESULT', 'citation': 'Neskovic-Konstantinovic Z, Nooij M, Khaled H, et al.: Safety and efficacy of combined trastuzumab and CMF therapy in women with metastatic breast cancer: EORTC protocol 10995. [Abstract] J Clin Oncol 25 (Suppl 18): A-1040, 2007.'}, {'pmid': '28324265', 'type': 'DERIVED', 'citation': 'Tryfonidis K, Marreaud S, Khaled H, De Valk B, Vermorken J, Welnicka-Jaskiewicz M, Aalders K, Bartlett JMS, Biganzoli L, Bogaerts J, Cameron D; EORTC- Breast Cancer Group. Cardiac safety, efficacy, and correlation of serial serum HER2-extracellular domain shed antigen measurement with the outcome of the combined trastuzumab plus CMF in women with HER2-positive metastatic breast cancer: results from the EORTC 10995 phase II study. Breast Cancer Res Treat. 2017 Jun;163(3):507-515. doi: 10.1007/s10549-017-4203-y. Epub 2017 Mar 21.'}]}, 'descriptionModule': {'briefSummary': 'RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, methotrexate, and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with trastuzumab may kill more tumor cells.\n\nPURPOSE: Phase II trial to study the effectiveness of combining combination chemotherapy with trastuzumab in treating women who have metastatic breast cancer.', 'detailedDescription': 'OBJECTIVES:\n\n* Compare the incidence of clinical heart failure in women with c-erbB2-positive metastatic breast cancer treated with cyclophosphamide, methotrexate, and fluorouracil in combination with trastuzumab (Herceptin®).\n* Compare the therapeutic activity of this regimen, in terms of objective response rate, in these patients.\n* Compare the duration of response and time to progression in patients treated with this regimen.\n* Compare the toxic effects of this regimen in these patients.\n\nOUTLINE: This is a multicenter study.\n\nPatients receive CMF comprising cyclophosphamide orally on days 1-14 or IV on days 1 and 8 and methotrexate IV and fluorouracil IV on days 1 and 8. Patients also receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day 1. Treatment repeats every 4 weeks for 8 courses. Patients then receive trastuzumab once every 3 weeks in the absence of disease progression, unacceptable toxicity, or patient refusal.\n\nPatients are followed every 8 weeks until documentation of disease progression or initiation of a new anticancer therapy. Patients developing disease progression are followed every 12 weeks.\n\nPROJECTED ACCRUAL: A total of 66 patients will be accrued for this study within 2 years.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '120 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'DISEASE CHARACTERISTICS:\n\n* Histologically confirmed metastatic breast cancer c-erbB2 positive (3+ overexpression by the HercepTest™ method) in the primary tumor or metastatic site\n* At least 1 unidimensionally measurable target lesion\n\n * At least 20 mm by conventional techniques OR\n * At least 10 mm by spiral CT scan\n * Lesions that have been irradiated in the preceding 3 months cannot be used as target lesions unless they have appeared or clearly progressed since prior irradiation\n * No bone lesions as the only target lesions\n* No contralateral breast cancer that is c-erbB2-positive or c-erbB2-negative/unknown, with status determined on a metastatic site\n* No CNS metastases\n\n * CT scan of brain and CSF cytology are required if neurologic symptoms are present\n* Hormone receptor status:\n\n * Any estrogen or progesterone receptor status\n\nPATIENT CHARACTERISTICS:\n\nAge:\n\n* 18 and over\n\nSex:\n\n* Female\n\nMenopausal status:\n\n* Any status\n\nPerformance status:\n\n* ECOG 0-2\n\nLife expectancy:\n\n* Not specified\n\nHematopoietic:\n\n* Neutrophil count at least 1,500/mm\\^3\n* Platelet count at least 100,000/mm\\^3\n\nHepatic:\n\n* Bilirubin no greater than 1.25 times upper limit of normal (ULN)\n* Transaminases less than 2.5 times ULN (5 times ULN if liver metastases present)\n\nRenal:\n\n* For patients age 18 to 69:\n\n * Creatinine no greater than ULN\n* For patients age 70 and over:\n\n * Creatinine clearance normal\n\nCardiovascular:\n\n* LVEF normal by MUGA or echocardiogram\n* No clinical heart failure\n\nPulmonary:\n\n* No malignancy-associated dyspnea at rest\n* No requirement for supportive oxygen therapy\n\nOther:\n\n* Not pregnant or nursing\n* No other prior or concurrent malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer\n* No psychological, familial, sociological, or geographical condition that would preclude compliance with study therapy and follow-up schedule\n\nPRIOR CONCURRENT THERAPY:\n\nBiologic therapy:\n\n* No prior anti-c-erbB2 antibody, including trastuzumab (Herceptin®)\n* No other concurrent biologic therapy\n\nChemotherapy:\n\n* No more than 1 prior chemotherapy regimen for metastatic breast cancer\n* Prior combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) allowed in the adjuvant or metastatic setting only if the disease-free interval after completion of CMF was at least 12 months\n* Prior anthracyclines and/or taxanes allowed\n* At least 4 weeks since prior anthracyclines\n* No prior cumulative dose of doxorubicin more than 360 mg/m\\^2\n* No prior cumulative dose of epirubicin more than 720 mg/m\\^2\n* No prior cumulative dose of mitoxantrone more than 90 mg/m\\^2\n* No other concurrent chemotherapy\n\nEndocrine therapy:\n\n* More than 2 weeks since prior hormonal therapy in the adjuvant or metastatic setting\n* No concurrent hormonal therapy\n\nRadiotherapy:\n\n* See Disease Characteristics\n* No concurrent radiotherapy\n\nSurgery:\n\n* Not specified\n\nOther:\n\n* No other concurrent anticancer therapy or investigational drugs\n* No concurrent bisphosphonates started after study enrollment except for hypercalcemia'}, 'identificationModule': {'nctId': 'NCT00036868', 'briefTitle': 'Combination Chemotherapy With Trastuzumab in Treating Women With Metastatic Breast Cancer', 'organization': {'class': 'NETWORK', 'fullName': 'European Organisation for Research and Treatment of Cancer - EORTC'}, 'officialTitle': 'A Randomized Phase II Study Of CMF Alone And In Combination With Anti c-erbB2 Antibody (Herceptin) In Women With c-erbB2 Positive Metastatic Breast Cancer', 'orgStudyIdInfo': {'id': 'EORTC-10995-16999'}, 'secondaryIdInfos': [{'id': 'EORTC-10995'}, {'id': 'EORTC-16999'}, {'id': 'IDBBC-EORTC-10995'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'CMF + Herceptin', 'interventionNames': ['Biological: trastuzumab', 'Drug: CMF regimen', 'Drug: cyclophosphamide', 'Drug: fluorouracil', 'Drug: methotrexate']}], 'interventions': [{'name': 'trastuzumab', 'type': 'BIOLOGICAL', 'armGroupLabels': ['CMF + Herceptin']}, {'name': 'CMF regimen', 'type': 'DRUG', 'armGroupLabels': ['CMF + Herceptin']}, {'name': 'cyclophosphamide', 'type': 'DRUG', 'armGroupLabels': ['CMF + Herceptin']}, {'name': 'fluorouracil', 'type': 'DRUG', 'armGroupLabels': ['CMF + Herceptin']}, {'name': 'methotrexate', 'type': 'DRUG', 'armGroupLabels': ['CMF + Herceptin']}]}, 'contactsLocationsModule': {'locations': [{'zip': '2020', 'city': 'Antwerp', 'country': 'Belgium', 'facility': 'Ziekenhuis Netwerk Antwerpen Middelheim', 'geoPoint': {'lat': 51.22047, 'lon': 4.40026}}, {'zip': '1000', 'city': 'Brussels', 'country': 'Belgium', 'facility': 'Institut Jules Bordet', 'geoPoint': {'lat': 50.85045, 'lon': 4.34878}}, {'zip': 'B-2650', 'city': 'Edegem', 'country': 'Belgium', 'facility': 'Universitair Ziekenhuis Antwerpen', 'geoPoint': {'lat': 51.15662, 'lon': 4.44504}}, {'zip': 'DK-2730', 'city': 'Copenhagen', 'country': 'Denmark', 'facility': 'Herlev Hospital - University Hospital of Copenhagen', 'geoPoint': {'lat': 55.67594, 'lon': 12.56553}}, {'city': 'Cairo', 'country': 'Egypt', 'facility': 'National Cancer Institute of Egypt', 'geoPoint': {'lat': 30.06263, 'lon': 31.24967}}, {'zip': '21079', 'city': 'Dijon', 'country': 'France', 'facility': 'Centre de Lutte Contre le Cancer Georges-Francois Leclerc', 'geoPoint': {'lat': 47.31344, 'lon': 5.01391}}, {'zip': '1091 HA', 'city': 'Amsterdam', 'country': 'Netherlands', 'facility': 'Onze Lieve Vrouwe Gasthuis', 'geoPoint': {'lat': 52.37403, 'lon': 4.88969}}, {'zip': '2300 CA', 'city': 'Leiden', 'country': 'Netherlands', 'facility': 'Leiden University Medical Center', 'geoPoint': {'lat': 52.15833, 'lon': 4.49306}}, {'zip': 'NL-6500 HB', 'city': 'Nijmegen', 'country': 'Netherlands', 'facility': 'Nijmegen Cancer Center at Radboud University Medical Center', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}, {'zip': '80-211', 'city': 'Gdansk', 'country': 'Poland', 'facility': 'Medical University of Gdansk', 'geoPoint': {'lat': 54.35227, 'lon': 18.64912}}, {'zip': '11000', 'city': 'Belgrade', 'country': 'Serbia', 'facility': 'Institute of Oncology and Radiology of Serbia', 'geoPoint': {'lat': 44.80401, 'lon': 20.46513}}, {'zip': '2193', 'city': 'Johannesburg', 'country': 'South Africa', 'facility': 'Medical Oncology Centre of Rosebank', 'geoPoint': {'lat': -26.20227, 'lon': 28.04363}}, {'zip': 'G11 6NT', 'city': 'Glasgow', 'state': 'Scotland', 'country': 'United Kingdom', 'facility': 'Western Infirmary', 'geoPoint': {'lat': 55.86515, 'lon': -4.25763}}], 'overallOfficials': [{'name': 'David Cameron', 'role': 'STUDY_CHAIR', 'affiliation': 'Western General Hospital, Edinburgh'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'European Organisation for Research and Treatment of Cancer - EORTC', 'class': 'NETWORK'}, 'responsibleParty': {'type': 'SPONSOR'}}}}