De-escalation Chemotherapies Versus Escalation in Non Pre-treated Unresectable Patients With Metastatic Colorectal Cancer

Sponsor
Federation Francophone de Cancerologie Digestive
Study ID
NCT02842580
Phase
PHASE2
Status
Terminated

Conditions

Eligibility Criteria

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

Interventions

  • 5 FLUOROURACYL — DRUG
    Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as a 2 hr infusion. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days. For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.
  • acide folinique — DRUG
    200 mg/m² if Elvorine
  • irinotecan — DRUG
    Irinotecan is administered IV at a dose of 180 mg/m² over 90 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with irinotecan. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.
  • Oxaliplatin — DRUG
    Oxaliplatin is administered IV at a dose of 85 mg/m² over 120 minutes. Folinic acid is administered IV at a dose of 400 mg/m² (or 200 mg/m² if Elvorine) as an infusion over 2 hours, to be given in Y along with oxaliplatin. The 5FU bolus is administered in less than 10 minutes at 400 mg/m² (on D1). The continuous 5FU is administered IV at a dose of 2400 mg/m² over 46 hr (D1 and D2). The cycles will last 14 days.
  • capécitabine — DRUG
    For this 1st line chemotherapy, the investigator has the choice of using capecitabine instead of LV5FU2; in this case the cycle lasts 21 days.
  • bevacizumab — DRUG
    Bevacizumab is administered IV at a dose of 5 mg/kg over 90 min at cycle 1, then 60 min at cycle 2 and 30 min in subsequent cycles. Bevacizumab is administered every 2 weeks before the start of chemotherapy

Study Details

The intensity of tumour response appears to be correlated with the feasibility and the duration of a therapeutic pause or of a reduced maintenance therapy maintained until progression in patients initially controlled by so-called "induction" chemotherapy. Bevacizumab combined with cytotoxic chemotherapy (5-FU, irinotecan and/or oxaliplatin) has shown that it is possible to improve the tumour response rate and patient prognosis in 1st and 2nd lines. With a very favourable safety profile , it is an excellent candidate as induction treatment and also as maintenance treatment. Prospective data from recent trials have actually demonstrated improvement in PFS and/or overall survival with bevacizumab maintenance alone or in combination with 5FU (or capecitabine) after induction chemotherapy (FOLFIRI or FOLFOX + bevacizumab). At the same time, the maintenance of anti-angiogenic pressure after progression in 1st line metastatic has demonstrated its benefit in terms of PFS and overall survival. Bevacizumab maintenance in 2nd line metastatic, despite progression, thus appears to be a valid strategy.

Key Dates

Start date
Sep 30, 2016
Status verified
Jul 2024
Primary completion
Oct 31, 2020
Completion
Oct 31, 2020

Study Design

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

Arms

  • Active Comparator: Standard arm (escalation strategy - arm A)
    LV5FU2 (5 FLUOROURACYL)+avastin. After progression: FOLFIRI + avastin. after the 2nd progression:FOLFOX4 (eloxatine)+ avastin.
  • Experimental: Experimental arm (de-escalation strategy -arm B)
    (4 cycles of FOLFOXIRI (campto) + avastin and 4 cycles of FOLFIRI + avastin) is followed by maintenance with capecitabine

Primary Outcome Measure

The Primary Objective Was the Percentage of Patients Without Failure of the Strategy 16 Months After the Randomization. [ Time Frame: 16 months after randomization ]

Related Studies