FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab 1st-line in BRAF-mutated mCRC

Sponsor
Ludwig-Maximilians - University of Munich
Study ID
NCT04034459
Phase
PHASE2
Status
Unknown

Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

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

Interventions

  • Bevacizumab — DRUG
    Bevacizumab 5 mg/kg BW iv over 30 to 90\* min day 1
  • Irinotecan — DRUG
    Irinotecan 150 mg/m² iv, 30 - 90 min. day 1
  • Folinic acid — DRUG
    Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1
  • Oxaliplatin — DRUG
    Oxaliplatin 85mg/m² day 1
  • 5-FU — DRUG
    5-FU 3000 mg/m² iv over 48 h days 1-2
  • Cetuximab — DRUG
    Cetuximab initially 400 mg/m² with infusion rate of ≤5 mg/min., subsequently 250 mg/m² iv with infusion rate of ≤10 mg/min. days 1+8

Study Details

Once randomisation has been completed, the study treatment should be started preferably immediately; at the latest within one week following randomisation. The patients will be randomised in a ratio of 1:2 to the following two treatment arms. Patients in both treatment arms will receive standard chemotherapy with FOLFOXIRI as background treatment, which can be de-escalated to FOLFIRI in case of toxicity. Standard arm A: The patient will be treated with FOLFOXIRI plus bevacizumab for up to 12 cycles (24 weeks) or until progression (if the latter occurs before completing the 12 cycles). Within the 12 cycles, the FOLFOXIRI plus bevacizumab regimen may be de-escalated, owing to toxicity, to FOLFIRI and bevacizumab at the treating physician's discretion. After 12 cycles of the study treatment, a switch to a maintenance regimen with a fluoropyrimidine (5-FU infusion or capecitabine) plus bevacizumab, administered until progression occurs, is recommended. The recommended maintenance phase of the study is not part of the study treatment. However, maintenance therapy will be counted as first-line therapy. Experimental arm B: The patient will be treated with FOLFOXIRI plus weekly administration of cetuximab for up to 12 cycles (24 weeks) or until progression (if the latter occurs before completing the 12 cycles). Within the 12 cycles, the FOLFOXIRI plus cetuximab regimen may be de-escalated owing to toxicity, to FOLFIRI and cetuximab at the treating physician's discretion. After 12 cycles, a switch to a maintenance regimen with 5-FU and cetuximab or with irinotecan and cetuximab, administered until progression occurs, is recommended. The recommended maintenance phase of the study is not part of the study treatment. However, maintenance therapy will be counted as first-line therapy.

Key Dates

Start date
Nov 25, 2016
Status verified
Nov 2023
Primary completion
Nov 1, 2023
Completion
Dec 31, 2023

Study Design

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

Arms

  • Active Comparator: FOLFOXIRI plus bevacizumab
    One cycle (cycle duration 14 days) consists of: * Irinotecan 150 mg/m² iv, 30 - 90 min. day 1 * Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1 * Oxaliplatin 85mg/m² day 1 * 5-FU 3000 mg/m² iv over 48 h days 1-2 * Bevacizumab 5 mg/kg BW iv over 30 to 90\* min day 1 \*1st administration 90 min.; in case of good tolerability, second administration 60 min.; further administrations 30 min. Repeat administration every 2 weeks for a maximum of 12 cycles * Dose adaptation at the treating physician's discretion. * Switch to the recommended maintenance treatment with fluoropyrimidine and bevacizumab after the 8th cycle (following 2nd staging after baseline) is possible at the treating physician's discretion if response according to RECIST 1.1 (CR or PR) has been achieved.
  • Experimental: FOLFOXIRI plus cetuximab
    One cycle (cycle duration 14 days) consists of: * Irinotecan 150 mg/m² iv, 30 - 90 min. day 1 * Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1 * Oxaliplatin 85mg/m² day 1 * 5-FU 3000 mg/m² iv over 48 h days 1-2 * Cetuximab initially 400 mg/m² with infusion rate of ≤5 mg/min., subsequently 250 mg/m² iv with infusion rate of ≤10 mg/min. days 1+8 Repeat administration every two weeks up to a maximum of 12 cycles. * Dose adaptation at the treating physician's discretion. * Switch to the recommended maintenance treatment with 5-FU and cetuximab or irinotecan and cetuximab after the 8th cycle (following 2nd staging after baseline) is possible at the treating physician's discretion if response according to RECIST 1.1 (CR or PR) has been achieved.

Primary Outcome Measure

Overall Response Rate (ORR) [ Time Frame: up to 48 months ]

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