RECRUITINGPhase 3INTERVENTIONAL

Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer

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

About This Trial

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. The 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.

Who May Be Eligible (Plain English)

Who May Qualify: 1. willing to sign a consent form signed before commencing any procedures related to the clinical trial. 2. Age ≥18 years. 3. ECOG status 0-2. 4. expected to live at least 12 weeks as assessed by the investigator. 5. Verified diagnosis of colorectal adenocarcinoma (C18.5, C19, C20). 6. 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). 7. Left-sided localization of the primary tumor (from the splenic flexure of the colon inclusive). 8. Verified wild type KRAS, NRAS determined from tumor tissue. 9. Satisfactory function of hematopoiesis and internal organs: - absolute number of neutrophils ≥ 1.5×10 9 /l; - platelet count at least 100×10 9 /l; - blood count (hemoglobin) at least 90 g/l. - creatinine clearance above 50 ml/min; - total bilirubin \<1.5 X the upper limit of normal; - 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. 10. 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. Who Should NOT Join This Trial: 1. Previous systemic therapy for metastatic disease. 2. Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status). 3. Uncertain KRAS/NRAS status 4. 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. 5. HIV infection, active hepatitis B, active hepatitis C. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Informed consent signed before commencing any procedures related to the clinical trial. 2. Age ≥18 years. 3. ECOG status 0-2. 4. Life expectancy greater than 12 weeks as assessed by the investigator. 5. Verified diagnosis of colorectal adenocarcinoma (C18.5, C19, C20). 6. 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). 7. Left-sided localization of the primary tumor (from the splenic flexure of the colon inclusive). 8. Verified wild type KRAS, NRAS determined from tumor tissue. 9. Satisfactory function of hematopoiesis and internal organs: * absolute number of neutrophils ≥ 1.5×10 9 /l; * platelets ≥ 100×10 9 /l; * hemoglobin ≥ 90 g/l. * creatinine clearance above 50 ml/min; * total bilirubin \<1.5 X the upper limit of normal; * 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. 10. 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. Exclusion Criteria: 1. Previous systemic therapy for metastatic disease. 2. Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status). 3. Uncertain KRAS/NRAS status 4. 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. 5. HIV infection, active hepatitis B, active hepatitis C. 6. Complicated primary tumor, requiring urgent surgical intervention. After it is eliminated, the patient can participate in the study. 7. The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the study. 8. Impossibility of organizing central venous access.

Treatments Being Tested

DRUG

Cetuximab

FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles

Locations (3)

Moscow Multidiciplinary Clinical Center Kommunarka

Moscow, Russia

N.N Blokhin Cancer Reserch Center

Moscow, Russia

Reutov Clinical hospital

Reutov, Russia