Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases

Sponsor
Dutch Colorectal Cancer Group
Study ID
NCT02162563
Phase
PHASE3
Status
Completed

Conditions

Eligibility Criteria

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

Interventions

  • FOLFOX/ FOLFIRI with bevacizumab — DRUG
    FOLFIRI + bevacizumab Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by irinotecan 180 mg/m2 i.v. in 60 minutes together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by bolus 5-fluorouracil 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks FOLFOX6 + bevacizumab Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by oxaliplatin 85 mg/m2 i.v. together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by bolus 5FU 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks
  • FOLFOXIRI with bevacizumab — DRUG
    FOLFOXIRI + bevacizumab Bevacizumab 5 mg/kg in 15-30 minutes i.v., followed by irinotecan 165 mg/m2 i.v. in 60 minutes, followed by oxaliplatin 85 mg/m2 i.v. together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by continuous infusion of 5-fluorouracil 3200 mg/m2 in 46 hours, every 2 weeks
  • FOLFOX/ FOLFIRI with panitumumab — DRUG
    FOLFIRI + panitumumab Panitumumab 6 mg/kg i.v. (1st dose in 60 minutes, if well tolerated subsequent doses in 30 minutes), followed by irinotecan 180 mg/m2 i.v. in 60 minutes together with leucovorin 400 mg/m2 i.v. in 120 minutes, followed by bolus 5-fluorouracil 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks FOLFOX6 + panitumumab Panitumumab 6 mg/kg i.v. (1st dose in 60 minutes, if well tolerated subsequent doses in 30 minutes), followed by oxaliplatin 85 mg/m2 i.v. together with leucovorin 400 mg/m2 i.v. in 120 minutes, and bolus 5FU 400 mg/m2 within 4 minutes, all on day 1, followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours, every 2 weeks

Study Details

Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and no consensus exist on criteria for resectability. In this study colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by an expert panel according to predefined criteria, will be tested for RAS and BRAF tumor mutation status and selected by location of primary tumor. Patients with RAS or BRAF mutant and/or right sided tumors will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab (schedule 1), and triple chemotherapy (FOLFOXIRI) plus bevacizumab (schedule 2). Patients with RAS AND BRAF wildtype AND left-sided primary tumors will be randomized between doublet chemotherapy (FOLFOX or FOLFIRI) plus either bevacizumab (schedule 1) or panitumumab (schedule 3). Patient imaging will be reviewed for resectability by a central panel, consisting of at least one radiologist and three surgeons every assessment. Central panel review will be performed prior to randomization as well as during treatment, as described in the protocol.

Key Dates

First listed
Jun 12, 2014
Start date
Jul 31, 2014
Status verified
Feb 2025
Primary completion
Jul 31, 2022
Completion
Jan 31, 2025

Study Design

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

Arms

  • Experimental: Arm B: FOLFOXIRI & bevacizumab (inclusion completed)
    Patients with RAS or BRAF mutated and/or right-sided tumors will receive 5FU, irinotecan, oxaliplatin (FOLFOXIRI) and bevacizumab. Intervention: FOLFOXIRI with bevacizumab
  • Active Comparator: Arm A: FOLFOX/FOLFIRI & bevacizumab (inclusion completed)
    Patients with RAS or BRAF mutated and/or right-sided tumors will receive doublet fluoropyrimidine-containing chemotherapy (FOLFOX or FOLFIRI), plus bevacizumab. Intervention: FOLFOX/FOLFIRI with bevacizumab
  • Experimental: Arm D: FOLFOX/FOLFIRI & panitumumab
    Patients with RAS and BRAF wildtype and left-sided tumors will receive doublet fluoropyrimidine-containing chemotherapy (FOLFOX or FOLFIRI), plus panitumumab. Intervention: FOLFOX/FOLFIRI with panitumumab
  • Active Comparator: Arm C: FOLFOX/ FOLFIRI & bevacizumab
    Patients with RAS and BRAF wildtype and left-sided tumors will receive doublet fluoropyrimidine-containing chemotherapy (FOLFOX or FOLFIRI), plus bevacizumab. Intervention: FOLFOX/FOLFIRI with bevacizumab

Primary Outcome Measure

Progression-free survival (PFS) [ Time Frame: 2 years after last patient in study ]

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