Chemotherapies Associated With Targeted Therapies on the Resection Rate of Hepatic Metastases

Sponsor
UNICANCER
Study ID
NCT01442935
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Oxaliplatin — DRUG
    85mg/m² over 120 mn every 2 weeks up to progression or toxicity
  • Folinic Acid — DRUG
    400mg/m² over 120 mn every 2 weeks up to progression or toxicity
  • 5-FU — DRUG
    400mg/m² in bolus, then 2400mg/m² over 46 h every 2 weeks up to progression or toxicity
  • Irinotecan — DRUG
    180mg/m² over 90 mn every 2 weeks up to progression or toxicity
  • Irinotecan — DRUG
    150mg/m² over 30-90 mn every 2 weeks up to progression or toxicity
  • Bevacizumab — DRUG
    5mg/kg over 90 mn every 2 weeks up to progression or toxicity
  • Cetuximab — DRUG
    500mg/m² over 90 mn every 2 weeks up to progression or toxicity

Study Details

The main objective is to compare resection rates (R0 or R1) for hepatic metastases in the experimental arm (tri chemotherapy plus targeted therapy) versus the control arm (bi chemotherapy plus targeted therapy); in both arms the targeted therapy is selected according to K-Ras status of the patient's tumor. The secondary objectives are to evaluate the objective response rate (CR and PR) after 4 cycles of treatment, according the RECIST V1.1 evaluation scale. * the rate of complete remission (CR) at 6 months after the last study treatment (hepatic surgery or last chemotherapy cycle). * the specific rates of resection R0, R1, R2. * the complete pathological response Rate, * the relapse-free survival rate in (R0 or R1) resected patients, * the response duration in non-resected patients, * the toxicity according to CTC AE V4 scale except for the neurotoxicity that will be evaluated with the Levi scale, * the post operative complications using the DINDO classification, * the progression-free survival (PFS) and overall survival (OS). The objectives of the biological study are: * to evaluate tumor-related predictive factors such as somatic mutations (KRAS, BRAF, TP53) and genetic amplification related factors (EGFR), * to evaluate patient-related predictive factors in connection with genetic polymorphisms (Fc gamma and VEGF receptors), * to evaluate ADCC activity via immunohistochemistry in order to analyze the lympho free and progression-free survival, * to study circulating of tumor cells as prognostic factor for metastatic colorectal cancer, non- resectable at presentation.

Key Dates

Start date
Feb 28, 2011
Status verified
Jun 2021
Primary completion
Dec 31, 2015
Completion
Jan 31, 2021

Study Design

Enrollment
256 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Arm A1 : Folfiri + targeted therapy
    Every 2 weeks : * irinotecan 180 mg/m² D1 * Folinic acid 400 mg/m² D1 * 5FU 400 mg/m² bolus * 5FU 2400 mg/m² infusion over 46 h, D1 And targeted therapy in function of Kras: * For mutated Kras = bevacizumab: 5 mg/kg IV on D1 of each cycle of chemotherapy, every 14 days * For non-mutated Kras = cetuximab : 500 mg/m² IV, on D1 of each cycle of chemotherapy, every 14 days.
  • Active Comparator: Arm A2 : Folfox 4 + targeted therapy
    Every 2 weeks : * oxaliplatin 85 mg/m² D1 * Folinic acid 400 mg/m² D1 * 5FU 400 mg/m² bolus * 5FU 2400 mg/m² infusion over 46 h, D1 And targeted therapy in function of Kras: * For mutated Kras = bevacizumab: 5 mg/kg IV on D1 of each cycle of chemotherapy, every 14 days * For non-mutated Kras = cetuximab : 500 mg/m² IV, on D1 of each cycle of chemotherapy, every 14 days.
  • Experimental: Arm B : Folfirinox + targeted therapy
    Every 2 weeks : * oxaliplatin 85 mg/m² D1 * irinotecan 150 mg/m² D1 * Folinic acid 400 mg/m² D1 * 5FU 400 mg/m² bolus * 5FU 2400 mg/m² infusion over 46 h, D1. From D7 to D12, prophylactic G-CSF such as Granocyte® will be administered. And targeted therapy in function of Kras: * For mutated Kras = bevacizumab: 5 mg/kg IV on D1 of each cycle of chemotherapy, every 14 days * For non-mutated Kras = cetuximab : 500 mg/m² IV, on D1 of each cycle of chemotherapy, every 14 days.

Primary Outcome Measure

The main objective is to compare resection rates (R0 or R1) for hepatic metastases [ Time Frame: at least 4-6 weeks after the end of chemotherapy ]

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