Sequential Treatment Strategy for Metastatic Colorectal Cancer

Sponsor
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Study ID
NCT01878422
Phase
PHASE3
Status
Completed

Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

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

Interventions

Study Details

Study Design: This is a pragmatic study on the management strategy for patients with metastatic colorectal cancer (CRC) who are candidates for CT, independently of any previous adjuvant therapy received. The aim of this study is to define the role of new target molecules in combination with CT in first- and second line treatment. First line study: Eligible patients were randomized to either treatment: Arm A: FOLFIRI or FOLFOX + Bevacizumab, cycle to be repeated every 2 weeks * BEVACIZUMAB: Day 1,1st cycle 5 mg/kg IV infusion of 90 min Day 1, 2nd cycle if well tolerated, 5 mg/kg IV infusion of 60 min Day 1, 3rd cycle and subsequent cycles if well tolerated, 5 mg/kg IV infusion of 30 min after 5-Fluorouracile (FU) bolus * FOLFIRI Day 1: Irinotecan 180 mg/m2 IV infusion 30-90 min Day 1,2: L-Folinic acid 100 mg/m2 IV infusion of 2 hours 5-Fluorouracil 400 mg/m2 as a bolus 5-Fluorouracil 600 mg/m2 continuous IV infusion of 22 hours - FOLFOX Day 1: Oxaliplatin 85 mg/m2 IV infusion of 2hours Day 1,2: L-Folinic acid 100 mg/m2 IV infusion of 2 hours 5-Fluorouracil 400 mg/m2 as a bolus 5-Fluorouracil 600 mg/m2 continuous IV infusion of 22 hours Arm B: FOLFIRI or FOLFOX, cycle to be repeated every 2 weeks If FOLFIRI: FOLFIRI as specified in arm A without Bevacizumab If FOLFOX: FOLFOX as specified in arm A without Bevacizumab Duration of Therapy For both arms, CT was repeated until progressive disease (PD) or unacceptable toxicity occurs. If unacceptable CT-related toxicity occurs in ARM A, in the absence of PD patients stopped CT and continued with only bevacizumab 5 mg/kg as a 30-min infusion every 2 weeks until progression or intolerable toxicity occurred. Second line - it is divided in two different studies (2A and 2B): Study 2A: Patients from arm A and Kras Wild Type were randomized to: * Arm C: FOLFIRI or FOLFOX (the CT schedule not received in 1st line trial, as defined in arm B) * Arm D: FOLFIRI or FOLFOX (the CT schedule not received in 1st line trial, as described in arm B) plus CETUXIMAB CETUXIMAB 1st cycle Day 1 400 mg/m2 infusion of 120 min 2 hrs before CT infusion 1st cycle Day 8 and subsequent cycles 250 mg/m2 infusion of 60 min 1 hr before CT infusion Patients from arm A and Kras Mutant were treated according to arm C. Study 2B: Patients from arm B and Kras Wild Type were randomized to: * Arm E: FOLFIRI or FOLFOX (the CT schedule not received in the 1st line trial, as defined in arm B) plus BEVACIZUMAB * Arm F: FOLFIRI or FOLFOX (the CT schedule not received in the first-line trial, as defined in arm B) plus BEVACIZUMAB and CETUXIMAB; cycle to be repeated every 2 weeks, whilst cetuximab will be administered weekly. * BEVACIZUMAB 2nd day of 1st cycle 5 mg/kg IV infusion of 90 min 2nd day of 2 nd cycle if well tolerated, 5 mg/kg IV infusion of 60 min 2nd day of 3 rd cycle and subsequent cycles if well tolerated, 5 mg/kg IV infusion of 30 min after the end of 5-FU bolus on the 2nd day * CETUXIMAB 1st cycle Day 1 400 mg/m2 infusion of 120 min 2 hr before CT infusion 1st cycle Day 8 and subsequent cycles 250 mg/m2 infusion of 60 min 1 hr before CT infusion If cetuximab will be stopped for any of the reasons specified in this protocol, bevacizumab will be administered as defined in arm A of the 1st line study Patients from arm B and Kras Mutant were treated according to arm E. Objectives of study The primary objective of the 1st line study is to determine whether the addition of bevacizumab to a poly-chemotherapy (polyCT) regimen (FOLFIRI or FOLFOX) improves efficacy in terms of progression-free survival (PFS). The secondary objectives of the 1st line study are to determine the Overall Response Rate (ORR) and the safety profile of the treatments administered. The primary objective of the 2nd line studies is to determine, separately for each study, whether the addition of cetuximab to a polyCT schemes (FOLFOX or FOLFIRI), or to polyCT schemes plus bevacizumab, improves efficacy in terms of PFS.The secondary objectives of the 2nd line studies are to determine the ORR, the overall survival (OS) and the safety profile of the treatments administered.

Key Dates

First listed
Jun 17, 2013
Start date
Nov 30, 2007
Status verified
Jan 2025
Primary completion
Mar 31, 2014
Completion
Jun 11, 2016

Study Design

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

Arms

  • Experimental: Arm A: FOLFIRI or FOLFOX + Bevacizumab
    * BEVACIZUMAB: Day 1,1st cycle 5 mg/kg IV infusion of 90 min Day 1, 2nd cycle if well tolerated, 5 mg/kg IV infusion of 60 min Day 1, 3rd cycle and subsequent cycles if well tolerated, 5 mg/kg IV infusion of 30 min after 5-FU bolus * FOLFIRI Day 1: Irinotecan 180 mg/m2 IV infusion 30-90 min Day 1,2: L-Folinic acid 100 mg/m2 IV infusion of 2 hours 5-Fluorouracil 400 mg/m2 as a bolus 5-Fluorouracil 600 mg/m2 continuous IV infusion of 22 hours \- FOLFOX Day 1: Oxaliplatin 85 mg/m2 IV infusion of 2hours Day 1,2: L-Folinic acid 100 mg/m2 IV infusion of 2 hours 5-Fluorouracil 400 mg/m2 as a bolus 5-Fluorouracil 600 mg/m2 continuous IV infusion of 22 hours
  • Experimental: Arm B: FOLFIRI or FOLFOX
    If FOLFIRI: FOLFIRI as specified in arm A without Bevacizumab If FOLFOX: FOLFOX as specified in arm A without Bevacizumab
  • Experimental: Arm C: FOLFIRI or FOLFOX
    Arm C: FOLFIRI or FOLFOX: for patients from arm A: FOLFIRI or FOLFOX (the CT schedule not received in 1st line trial, as defined in arm B)
  • Experimental: Arm D: FOLFIRI or FOLFOX plus CETUXIMAB
    Arm D: FOLFIRI or FOLFOX plus CETUXIMAB: for patients from arm B: FOLFIRI or FOLFOX (the CT schedule not received in 1st line trial, as described in arm B) plus CETUXIMAB
  • Experimental: Arm E: FOLFIRI or FOLFOX plus BEVACIZUMAB
    for patients from arm B: FOLFIRI or FOLFOX (the CT schedule not received in the 1st line trial, as defined in arm B) plus BEVACIZUMAB
  • Experimental: Arm F: FOLFIRI or FOLFOX plus BEVACIZUMAB and CETUXIMAB;
    for patients from arm B: FOLFIRI or FOLFOX (the CT schedule not received in the first-line trial, as defined in arm B) plus BEVACIZUMAB and CETUXIMAB; cycle to be repeated every 2 weeks, whilst cetuximab will be administered weekly.

Primary Outcome Measure

Progression Free Survival (PFS) of first and second line treatment strategy [ Time Frame: 6 years ]

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