Ignite Creation Date:
2025-12-24 @ 6:34 PM
Ignite Modification Date:
2025-12-30 @ 5:04 AM
Study NCT ID:
NCT06226857
Status:
RECRUITING
Last Update Posted:
2024-01-29
First Post:
2024-01-18
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type 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': 'D000068818', 'term': 'Cetuximab'}, {'id': 'D000077544', 'term': 'Panitumumab'}], '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': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'randomize and compare contol and experimental groups'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 355}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-01-17', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-01', 'completionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-01-25', 'studyFirstSubmitDate': '2024-01-18', 'studyFirstSubmitQcDate': '2024-01-18', 'lastUpdatePostDateStruct': {'date': '2024-01-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-01-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'progression-free survival', 'timeFrame': 'through study completion, an average of 3 years', 'description': 'Intention to treat, Calculated from start of therapy to date of disease progression or death'}], 'secondaryOutcomes': [{'measure': 'edverse events', 'timeFrame': 'through study completion, an average of 3 years', 'description': 'all AE based on CTC criteria v. 5'}, {'measure': 'overall survival', 'timeFrame': 'through study completion, an average of 3 years', 'description': 'Calculated from start of therapy to date of last contact or death'}, {'measure': 'progression-free survival based (per protocol)', 'timeFrame': 'through study completion, an average of 3 years'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Colorectal Neoplasms', 'Chemotherapy Effect', 'Molecular Sequence Variation']}, 'descriptionModule': {'briefSummary': 'Patients meeting the inclusion criteria will be randomized 1:1 into Cohort A (n ≈ 177) or Cohort BC (n ≈ 177). Cohort A is the control: patients receive combination chemotherapy with FOLFOX plus anti-EGFR therapy (panitumumab or cetuximab) based on RAS/BRAF wild-type data, according to clinical guidelines.\n\nThe BC cohort begins FOLFOX chemotherapy and simultaneously undergoes extensive molecular genetic profiling. Further, the BC cohort, depending on the profile, is divided into cohort B - patients without changes in alternative oncogenes, and cohort C - with changes in alternative oncogenes. The expected cohort ratio is 3:1 (\\~120 and \\~40 patients). Cohort B begins to receive anti-EGFR therapy in addition to chemotherapy, and the potentially resistant cohort C continues to receive chemotherapy alone or begins to receive bevacizumab if there are no contraindications.', 'detailedDescription': 'In total, the study plans to include 355 patients diagnosed with unresectable metastatic colorectal cancer with a left-sided localization of the primary tumor, who have not previously received systemic therapy for metastatic disease, have wild-type KRAS/NRAS/BRAF, or have wild-type KRAS/NRAS with unknown BRAF status in no contraindications to targeted therapy (cetuximab/panitumumab/bevacizumab).\n\nPatients meeting the inclusion criteria will be randomized 1:1 into Cohort A (n ≈ 177) or Cohort BC (n ≈ 177). Cohort A is the control: patients receive combination chemotherapy with FOLFOX plus anti-EGFR therapy (panitumumab or cetuximab) based on RAS/BRAF wild-type data, according to clinical guidelines. Next, this cohort, after completion of the protocol, undergoes extended profiling, according to the results of which it is divided into cohorts A1 and A2. Cohort A1 includes patients without changes in alternative oncogenes (N ≈ 120), cohort A2 includes patients with changes (N ≈ 40).\n\nThe BC cohort begins FOLFOX chemotherapy and simultaneously undergoes extensive molecular genetic profiling. Further, the BC cohort, depending on the profile, is divided into cohort B - patients without changes in alternative oncogenes, and cohort C - with changes in alternative oncogenes. The expected cohort ratio is 3:1 (\\~120 and \\~40 patients). Cohort B begins to receive anti-EGFR therapy in addition to chemotherapy, and the potentially resistant cohort C continues to receive chemotherapy alone or begins to receive bevacizumab if there are no contraindications.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Informed consent signed before commencing any procedures related to the clinical trial.\n2. Age ≥18 years.\n3. ECOG status 0-2.\n4. Life expectancy greater than 12 weeks as assessed by the investigator.\n5. Verified diagnosis of colorectal adenocarcinoma (C18.5, C19, C20).\n6. Metastatic unresectable form of the disease that has not previously received any systemic therapy for the metastatic process (previous neo-/adjuvant therapy completed at least 6 months before the detection of metastases is allowed).\n7. Left-sided localization of the primary tumor (from the splenic flexure of the colon inclusive).\n8. Verified wild type KRAS, NRAS determined from tumor tissue.\n9. Satisfactory function of hematopoiesis and internal organs:\n\n * absolute number of neutrophils ≥ 1.5×10 9 /l;\n * platelets ≥ 100×10 9 /l;\n * hemoglobin ≥ 90 g/l.\n * creatinine clearance above 50 ml/min;\n * total bilirubin \\<1.5 X the upper limit of normal;\n * ALT or AST \\>5 X the upper limit of normal in the presence of liver metastases or \\>2.5 X the upper limit of normal in the absence of liver metastases.\n10. Availability of a sufficient amount of tumor material for molecular genetic research. Tumor material must be collected no more than 24 months before inclusion in the study.\n\nExclusion Criteria:\n\n1. Previous systemic therapy for metastatic disease.\n2. Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status).\n3. Uncertain KRAS/NRAS status\n4. The presence of any other malignant tumor, with the exception of radically treated basal cell carcinoma, cervical cancer in situ, currently or within 5 years before inclusion in the study. Pregnant and lactating women, as well as planning pregnancy during the period of therapy in a clinical trial and 6 months after the end of therapy.\n5. HIV infection, active hepatitis B, active hepatitis C.\n6. Complicated primary tumor, requiring urgent surgical intervention. After it is eliminated, the patient can participate in the study.\n7. The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the study.\n8. Impossibility of organizing central venous access.'}, 'identificationModule': {'nctId': 'NCT06226857', 'acronym': 'CRC01', 'briefTitle': 'Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer', 'organization': {'class': 'OTHER_GOV', 'fullName': 'City Clinical Oncology Hospital No 1'}, 'officialTitle': 'Predictive Value of Other Oncogene Mutations for Anti-EGFR Monoclonal Antibodies Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer: Multicenter Randomized Phase III Trial', 'orgStudyIdInfo': {'id': 'CRC01'}, 'secondaryIdInfos': [{'id': '2102-2/23', 'type': 'OTHER_GRANT', 'domain': 'Moscow Center for healthcare innovations'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'A', 'description': 'All patients will recieve chemotherapy FOLFOX (oxaliplatin 85 mg/m2 + folinic acid 400 mg/m2 + FU 400 mg/m2 bolus and FU 2400 mg/m2 46-hour insusion q2w) + anti-EGFR monoclonal antibody (cetuximab 500 mg/m2 q2w or panitumumab 6 mg/kg q2w) until disease progression or unacceptable toxicity. It is permited to withdraw oxaliplatin after 8 cycles.', 'interventionNames': ['Drug: Cetuximab']}, {'type': 'EXPERIMENTAL', 'label': 'BC', 'description': 'All patients will recieve chemotherapy FOLFOX (oxaliplatin 85 mg/m2 + folinic acid 400 mg/m2 + FU 400 mg/m2 bolus and FU 2400mg/m2 46-hour insusion q2w). Monoclonal antibody will be added to chemotherapy after 1-2 cycles based on molecular profile results: anti-EGFR (cetuximab 500 mg/m2 q2w or panitumumab 6 mg/kg q2w) for hyperselected wild type tumors or bevacizumab 5 mg/m2 q2w for mutant profile.\n\nPatients will recieve therapy until disease progression or unacceptable toxicity. It is permited to withdraw oxaliplatin after 8 cycles.', 'interventionNames': ['Drug: Cetuximab']}], 'interventions': [{'name': 'Cetuximab', 'type': 'DRUG', 'otherNames': ['panitumumab'], 'description': 'FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles', 'armGroupLabels': ['A', 'BC']}]}, 'contactsLocationsModule': {'locations': [{'zip': '108814', 'city': 'Moscow', 'status': 'RECRUITING', 'country': 'Russia', 'contacts': [{'name': 'Mikhail Fedianin, phD', 'role': 'CONTACT', 'email': 'fedianinmu@mail.ru'}], 'facility': 'Moscow Multidiciplinary Clinical Center Kommunarka', 'geoPoint': {'lat': 55.75204, 'lon': 37.61781}}, {'zip': '115478', 'city': 'Moscow', 'status': 'RECRUITING', 'country': 'Russia', 'contacts': [{'name': 'Alexey Tryakin, phD', 'role': 'CONTACT', 'email': 'atryakin@gmail.com', 'phone': '+74993249834'}], 'facility': 'N.N Blokhin Cancer Reserch Center', 'geoPoint': {'lat': 55.75204, 'lon': 37.61781}}, {'zip': '143964', 'city': 'Reutov', 'status': 'RECRUITING', 'country': 'Russia', 'contacts': [{'name': 'Mikhail Byakhov, PhD', 'role': 'CONTACT', 'email': 'biakhovamm@mail.ru', 'phone': '+7-800-550-50-30'}], 'facility': 'Reutov Clinical hospital', 'geoPoint': {'lat': 55.76273, 'lon': 37.86303}}], 'centralContacts': [{'name': 'Ilya Pokataev, phD', 'role': 'CONTACT', 'email': 'pokia@mail.ru', 'phone': '+74955369406', 'phoneExt': '2007'}, {'name': 'Maria Byakhova, phD', 'role': 'CONTACT', 'email': 'biakhovamm@mail.ru', 'phone': '+79151751299'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'City Clinical Oncology Hospital No 1', 'class': 'OTHER_GOV'}, 'collaborators': [{'name': 'Atlas Biomed', 'class': 'INDUSTRY'}, {'name': 'N.N. Blokhin National Medical Research Center of Oncology', 'class': 'OTHER'}, {'name': 'Moscow MultidisciplinaryClinical Center Kommunarka', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Head of department of medical oncology', 'investigatorFullName': 'Pokataev Ilya', 'investigatorAffiliation': 'City Clinical Oncology Hospital No 1'}}}}