Folfoxiri Plus Bev Followed by Reintroduction of Folfoxiri Plus Bev at Progression Versus Folfox Plus Bev Followed by Folfiri Plus Bev in mCRC

Sponsor
Gruppo Oncologico del Nord-Ovest
Study ID
NCT02339116
Phase
PHASE3
Status
Unknown

Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

Study Details

Bev improves the efficacy of first-line chemotherapy in unresectable mCRC. In the phase III TRIBE trial upfront FOLFOXIRI plus bev provided a significant advantage in terms of PFS and RR compared to FOLFIRI plus bev. A trend toward better OS was also evidenced. The second-line treatment was at investigator's choice. A manageable increase in diarrhea, mucositis and neutropenia was reported, while no differences in febrile neutropenia, serious adverse events and toxic deaths were evidenced. A growing amount of data support the clinical relevance of achieving an early and deep tumor shrinkage. Phase III TML and BEBYP trials demonstrated that the continuation of bev beyond disease progression combined with a switched chemotherapy regimen provided a significant advantage in terms of OS and PFS. Based on recent evidences, the partial interruption of the upfront "induction" chemotherapy before disease progression and the prosecution of bev until disease progression as maintenance treatment is a valid strategy in the treatment of mCRC. On the basis of these considerations, a first-line doublet plus bev followed by a second-line switched doublet (from oxaliplatin to irinotecan and viceversa) plus bev should be considered a standard option for mCRC patients. Only retrospectively collected data are currently available about the efficacy of first-line FOLFOXIRI plus bev followed by second-line rechallenge with FOLFOXIRI plus bev. We therefore designed the present phase III randomized trial of first-line FOLFOXIRI plus bev followed by reintroduction of FOLFOXIRI plus bev at progression versus FOLFOX plus bev followed by FOLFIRI plus bev at progression in first- and second-line treatment of unresectable mCRC patients.

Key Dates

Start date
Feb 26, 2015
Status verified
Feb 2020
Primary completion
May 15, 2017
Completion
Feb 28, 2021

Study Design

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

Arms

  • Experimental: Folfoxiri/bev --> folfoxiri/bev
    FOLFOXIRI plus bev (to be repeated every 2 weeks for a maximum of 8 cycles): Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Irinotecan 165 mg/sqm iv over 60 minutes, day 1 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1 At the time of disease progression, patients will re-introduce FOLFOXIRI plus bev at the same doses and schedule previously tolerated, for a maximum of 8 cycles. If no progression occurs during FOLFOXIRI plus bev, patients will receive maintenance 5-FU/LV plus bev at the same dose used in the last cycle of the induction treatment.
  • Active Comparator: folfox/bev-->folfiri/bev
    mFOLFOX-6 plus bev (to be repeated every 2 weeks for a maximum of 8 cycles) Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluoruracil 400 mg/sqm iv bolus, day 1 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1 At the time of disease progression patients will receive FOLFIRI plus bev (to be repeated every 2 weeks for a maximum of 8 cycles): Bevacizumab 5 mg/kg iv over 30 minutes, day 1 Irinotecan 180 mg/sqm iv over 2 hours, day 1 L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 5-fluoruracil 400 mg/sqm iv bolus, day 1 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion.

Primary Outcome Measure

Progression Free Survival 2 (PFS2) [ Time Frame: from randomization to the first of the following events: a) death; b) disease progression on any treatment given after 1st progression, up to 18 months after last patient last visit ]

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