Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal Cancer Restricted to the Liver

Sponsor
Federation Francophone de Cancerologie Digestive
Study ID
NCT02885753
Phase
PHASE3
Status
Recruiting
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Conditions

Eligibility Criteria

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

Interventions

  • Oxaliplatin intravenous — DRUG
    85 mg/m² in intravenous. 1 cycle each 15 days
  • 5 FU bolus — DRUG
    5 fluorouracil : 400 mg/m² in bolus of 10 minutes (intravenous) following by 2400 mg/m² during 46 hours in intravenous
  • Folinic acid — DRUG
    400 mg/m² in intravenous
  • Oxaliplatin intra-arteriel — DRUG
    85 mg/m² in intra-arterial. 1 cycle each 15 days
  • Panitumumab — DRUG
    Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous
  • Bevacizumab — DRUG
    5 mg/kg at each cycle in intravenous
  • 5 FU continuous — DRUG
    2400 mg/m² intravenously over 46 hours
  • Irinotecan — DRUG
    150 mg/m² intravenous

Study Details

Colorectal cancer is the 3rd most common cancer in France and the 2nd cause of death from cancer. Between 30 to 60% of patients develop limited or predominant liver metastases. Surgical resection of these metastases, only curative treatment is not immediately possible in 10-15% of cases. In unresectable patients, current palliative treatments are based on systemic chemotherapy associated or not with the targeted therapies (anti-EGFR (panitumumab), anti-VEGF (bevacizumab)). In this patient population, special attention was paid to intensified treatment regimens in order to improve their efficiency and improving the tumoral response rate, the intensity of the response and its earliness correlate with improved overall and progression-free survival. The intra-arterial use of oxaliplatin coupled with IV chemotherapy has yielded OR levels of 64% in patients having survived one or more lines of chemotherapy IV and 62% in patients who have progressed on oxaliplatin IV. In addition, the HIA administration of oxaliplatin limits systemic and especially neurological toxicities, thanks to a greater hepatic clearance. In conclusion, the combination of systemic chemotherapy, targeted therapy and HIAC with oxaliplatin has showed promising efficacy results associated with good tolerance from the first line onwards. Indeed, we can expect from the Phase II recent data, a control rate close to 100%, with high response rates associated with early maturity and depth responses as well as prolonged survival. However, to date, in the absence of randomized trial testing this combination, this strategy does not have sufficient evidence to be integrated in our routine practices, and HIAC remains limited to a few expert centers in treatment catch-up.

Key Dates

Start date
Dec 31, 2016
Status verified
Jul 2025
Primary completion
Sep 30, 2028
Completion
Sep 30, 2028

Study Design

Enrollment
348 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental arm FOLFOX with oxaliplatin intraarterial + targeted therapy to RAS status
    Panitumumab (6 mg/kg if RAS wild) or Bevacizumab (5 mg/Kg if RAS mutated) Oxaliplatin (85 mg/m²) intraarterially Folinic Acid (400 mg/m²) intravenously 5Fu: 400 mg/m² in bolus of 10 minutes 5Fu: 2400 mg/m² intravenously over 46 hours
  • Active Comparator: Reference arm FOLFOX with oxaliplatin intravenous + targeted therapy to RAS status
    Panitumumab (6 mg/kg if RAS wild) or Bevacizumab (5 mg/Kg if RAS mutated) Oxaliplatin (85 mg/m²) intravenously Folinic Acid (400 mg/m²) intravenously 5Fu: 400 mg/m² in bolus of 10 minutes 5Fu: 2400 mg/m² intravenously over 46 hours
  • Experimental: Experimental arm mFOLFIRINOX with oxaliplatin intraarterial + Bevacizumab
    Bevacizumab (5 mg/Kg) Oxaliplatin (85 mg/m²) intraarterially Irinotecan (150 mg/m²) intravenously Folinic Acid (400 mg/m²) intravenously 5Fu: 2400 mg/m² intravenously over 46 hours
  • Active Comparator: Reference arm mFOLFIRINOX with oxaliplatin intravenous + Bevacizumab
    Bevacizumab (5 mg/Kg) Oxaliplatin (85 mg/m²) intravenously Irinotecan (150 mg/m²) intravenously Folinic Acid (400 mg/m²) intravenously 5Fu: 2400 mg/m² intravenously over 46 hours

Primary Outcome Measure

progression-free survival [ Time Frame: 24 months after randomization ]

Central Contacts

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