Ignite Creation Date:
2025-12-24 @ 2:32 PM
Ignite Modification Date:
2026-01-07 @ 6:59 PM
Study NCT ID:
NCT02821559
Status:
COMPLETED
Last Update Posted:
2016-07-01
First Post:
2016-03-29
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015179', 'term': 'Colorectal Neoplasms'}], 'ancestors': [{'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D003108', 'term': 'Colonic Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068258', 'term': 'Bevacizumab'}], '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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 37}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-03', 'lastUpdateSubmitDate': '2016-06-29', 'studyFirstSubmitDate': '2016-03-29', 'studyFirstSubmitQcDate': '2016-06-29', 'lastUpdatePostDateStruct': {'date': '2016-07-01', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-07-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Evolution of Raltitrexed plasma levels', 'timeFrame': 'at 5 minutes, at 40 minutes, at 2 hours, at 7,5 hours, at 24 hours and at 14 days after each raltitrexed administration', 'description': 'pharmacokinetic study'}], 'secondaryOutcomes': [{'measure': 'treatment-related adverse events as assessed by CTCAE v4.0', 'timeFrame': '3 months', 'description': 'comparison of number of treatment-related adverse events between two arms'}, {'measure': 'objective response rate evaluated by RECIST 1.1 criteria', 'timeFrame': '3 months'}, {'measure': 'progression-free survival (PFS)', 'timeFrame': 'through study completion, an average of 2 years', 'description': 'from date to randomization to date of first progression of the disease'}, {'measure': 'overall survival (OS)', 'timeFrame': 'through study completion, an average of 2 years', 'description': 'from date to randomization to date of death from any cause'}]}, 'conditionsModule': {'keywords': ['Colorectal cancer', 'raltitrexed', 'oxaliplatin', 'bevacizumab', 'biweekly', 'triweekly'], 'conditions': ['Metastatic Colorectal Cancer']}, 'descriptionModule': {'briefSummary': 'Raltitrexed is a potent thymidylate synthase (TS) inhibitor. Conversely to 5-fluorouracil (5FU), raltitrexed can be administered safely in patients with cardiovascular disease, as well as in patients with dihydropyrimidine dehydrogenase deficit. Since raltitrexed is administered in 15-minutes infusion, complications related to continuous infusion can be avoided, and it becomes a potential good candidate for locoregional treatments as hepatic intra-arterial or intra-peritoneal infusion. Despite these potential benefits over 5FU, clinical trials failed in their temptation to replace the 5FU in colorectal cancer patients, mainly due to raltitrexed toxicity at 3mg/m2 every 3 weeks. Oxaliplatin has demonstrated a synergic effect when combined with TS inhibitors, and its association with raltitrexed was evaluated at 130mg/m2 of oxaliplatin and 3mg/m2 of raltitrexed, every 3 weeks. Actually, one of the first-line standard regimens in metastatic colorectal cancer patients is the biweekly FOLFOX (85mg/m2 of oxaliplatin, and infusional 5FU) plus bevacizumab regimen, since a significant progression-free survival (PFS) benefit was observed over FOLFOX plus placebo. Biweekly administration of raltitrexed at 2mg/m2 demonstrated a favorable toxicity profile even in patients aged \\>65 years. Besides, the association of raltitrexed, oxaliplatin and bevacizumab seems safe.\n\nThen, the investigators decided to perform a randomized pharmacokinetic comparative study between biweekly TOMOX (raltitrexed 2 mg/m2 and oxaliplatin 85mg/m2) and triweekly TOMOX (raltitrexed 3 mg/m2 and oxaliplatin 130mg/m2) regimens in metastatic colorectal cancer patients, in a "ping-pong" crossover strategy to reduce the intra-individual variability. Bevacizumab was allowed at the dose of 5mg/kg or 7.5mg/kg, in biweekly and triweekly schedules, respectively. The secondary end-points were, objective response rate evaluated by RECIST 1.1 criteria, PFS, overall survival (OS), toxicity, and the comparison of toxicity between two arms for the first 2 cycles.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* performance status (ECOG-PS) of 0 or 1\n* patient with histologically proven colorectal cancer with distant metastases\n* measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1\n* life expectancy \\> 12 months\n* signed written informed consent\n\nExclusion Criteria:\n\n* prior chemotherapy at metastatic stage\n* presence of brain or meningeal metastases\n* other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix and squamous or basal cell carcinoma of the skin\n* preexisting peripheral neuropathy\n* known hypersensitivity to any component of the study treatment\n* any psychiatric condition compromising the understanding of information or conduct of the study\n* pregnancy, breast-feeding or absence of adequate contraception for fertile patients\n* patient under guardianship, curator or under the protection of justice'}, 'identificationModule': {'nctId': 'NCT02821559', 'acronym': 'EROS', 'briefTitle': 'Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer', 'organization': {'class': 'OTHER', 'fullName': 'Centre Hospitalier Universitaire de Besancon'}, 'orgStudyIdInfo': {'id': 'EROS'}, 'secondaryIdInfos': [{'id': '2011-005811-96', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'triweekly then biweekly', 'description': 'The arm A consisted of 2 cycles of triweekly TOMOX (standard dose 3mg/m2 of Raltitrexed in 15-minutes infusion, and 130mg/m2 of oxaliplatin in 2h infusion, every 3 weeks), followed by 2 cycles of biweekly TOMOX (2mg/m2 of Raltitrexed in 15-minutes infusion, and 85mg/m2 of oxaliplatin in 2h infusion, every 2 weeks).', 'interventionNames': ['Drug: TOMOX', 'Drug: Bevacizumab']}, {'type': 'EXPERIMENTAL', 'label': 'biweekly then triweekly', 'description': 'The arm B consisted of the reserve sequence starting with 2 cycles of biweekly TOMOX followed by 2 cycles of triweekly TOMOX regimen.', 'interventionNames': ['Drug: TOMOX', 'Drug: Bevacizumab']}], 'interventions': [{'name': 'TOMOX', 'type': 'DRUG', 'otherNames': ['Tomudex-Oxaliplatin', 'Raltitrexed-Oxaliplatin'], 'armGroupLabels': ['biweekly then triweekly', 'triweekly then biweekly']}, {'name': 'Bevacizumab', 'type': 'DRUG', 'description': 'Bevacizumab was allowed and used at 7,5 mg/kg or 5 mg/kg every 2 weeks.', 'armGroupLabels': ['biweekly then triweekly', 'triweekly then biweekly']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Besançon', 'country': 'France', 'facility': 'CHRU de Besançon', 'geoPoint': {'lat': 47.24878, 'lon': 6.01815}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Centre Hospitalier Universitaire de Besancon', 'class': 'OTHER'}, 'collaborators': [{'name': 'Hospira, now a wholly owned subsidiary of Pfizer', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}