Trial Comparing Two Two Sequences of Therapy in Colorectal Metastatic Patients
COMETS
Randomized, Phase III, Multicenter Trial Comparing Two Different Sequences of therapyFOLFOX-4 vs FOLFOX-4 Followed by Irinotecan/Cetuximab in Metastatic Colorectal Patients Treated With FOLFIRI /Bevacizumab as First Line Chemotherapy
1 other identifier
interventional
110
1 country
32
Brief Summary
Primary Objectives: Aim of this study is to compare the efficacy and safety of two different sequences of chemotherapeutic agents in order to optimize the treatment of patients with metastatic colorectal cancer progressed to a first line chemotherapy with FOLFIRI and bevacizumab. Primary endpoint will be overall survival, defined as the time elapsed from the date of randomization to the date of patient death due to any cause, or the last date the patient was known to be alive. Secondary Objectives Progression free survival, Quality of life, Health resource utilisation and economic evaluation, Toxicity and incidence of adverse events The study regimen includes: Strategy A: FOLFOX-4 followed, after progression, by irinotecan/cetuximab Strategy B: irinotecan/cetuximab followed, after progression, by FOLFOX-4 Patients will be randomly assigned to one of the two treatment sequences (with 1:1 ratio) using a block design randomization procedure stratified according to center. The patient accrual period is planned for approximately 36 months. To assess OS, all pts will be followed for up to 18 months after the last patient is randomised. The maximum estimated study duration is approximately 54 months.All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will be applied to describe study flow and protocol deviations.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Sep 2009
Longer than P75 for phase_3
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2009
CompletedFirst Submitted
Initial submission to the registry
December 9, 2009
CompletedFirst Posted
Study publicly available on registry
December 10, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2015
CompletedJuly 15, 2015
December 1, 2009
5.6 years
December 9, 2009
July 14, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival
the time from the date of randomisation to the date of death
Secondary Outcomes (1)
Progression free survival
the time relapsed from the date of randomization and the date of progression after third-line treatment or death
Study Arms (2)
Cetuximab/Irinotecan
EXPERIMENTALCetuximab/irinotecan followed, after progression, by FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil)
FOLFOX 4
ACTIVE COMPARATORFOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil) followed, after progression, by irinotecan/cetuximab
Interventions
Day 1: OXA will be administered as a 85 mg/m2 iv infusion over 2 hours; Leucovorin as a 100 mg/m2 infusion over 2 hours, 5-FU will be given as a 400 mg/m2 bolus injection, and then as a 600 mg/m2 continuous infusion over 22 hours after the first infusion Day 2: Leucovorin 100 mg/m2 (alone), followed by 5-FU 400 mg/m2 bolus injection, and 5-FU 600 mg/m2 continuous infusion after the first infusion Cycle length is 2 weeks comprising approximately 48 hours of infusion and 12 days of rest. Cycles are to be repeated every second week for a total of either 6 (12 weeks) or 12 cycles (24 weeks).
CET 400 mg/m2 intravenously via infusion pump given over a 120 min time and weekly CET infusions at a maintenance dose of 250 mg/m2 given over a 60 min time. IRI 180 mg/m2 iv infusion over 30-90 min. Cycle length is 2 weeks and it is to be repeated until disease progression.
Eligibility Criteria
You may qualify if:
- Age \>18 \<75 years of age
- Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
- K-ras wild-type
- Performance Status (ECOG-PS) 0-1 at study entry
- Neutrophils ≥ 1.5 x 1039/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL
- Bilirubin level either normal or \< 1.5 x upper limit of normal (ULN)
- Asparagine aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 X ULN (≤ 5 x ULN if liver metastasis are present)
- Serum creatinine \< 1.5 x ULN
- Effective contraception for both male and female patients
- Life expectancy of ≥ 3 months
- Signed written informed consent
You may not qualify if:
- History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
- Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
- History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake
- Known grade 3 or 4 allergic reaction to any of the components of the treatment
- Known drug abuse/ alcohol abuse
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (32)
A.O. Ospedale Umberto I - Università - Località Torretta
Ancona, Ancona, 60020, Italy
Ospedale Profili
Fabriano, AN, 60044, Italy
Usl 11 Ospedale Murri
Fermo, AP, 63023, Italy
Ospedali Riuniti, Largo Barozzi, 1
Bergamo, Bergamo, 24128, Italy
A.O. Treviglio-Caravaggio, P.le Ospedale n1
Treviglio, Bergamo, 24047, Italy
Fondazione Poliambulanza, Via Bissolati 57
Brescia, Brescia, 25100, Italy
Spedali Civili
Brescia, BS, 25100, Italy
AUSL di Lanciano-Vasto
Lanciano, CH, 66034, Italy
Istituto Oncologico del Mediterraneo
Catania, CT, 95029, Italy
ASL 11
Empoli, FI, 50010, Italy
Università
Florence, FI, 50139, Italy
A.O. Ospedale S.Anna
Como, Italy, 22100, Italy
Ospedale Maggiore
Lodi, LO, 26900, Italy
A.O. Carlo Poma - Via Albertoni, 1
Mantova, Mantova, 46100, Italy
Ospedale S.Vincenzo
Taormina, ME, 98039, Italy
Ospedale Serbelloni
Gorgonzola, MI, 20064, Italy
Istituto di Ricerca S.Raffaele
Milan, MI, 20100, Italy
Ospedale Fatebenefratelli
Milan, MI, 20100, Italy
A.O. S.Gerardo
Monza, MI, 20052, Italy
Istituto Oncologico Veneto
Padua, PD, 35124, Italy
A.O. S.Salvatore
Pesaro, PS, 61100, Italy
Ospedale Civile
Urbino, PS, 61029, Italy
Azienda Ospedaliera San Carlo
Potenza, PZ, 85100, Italy
Università Policlinico Umberto I
Roma, RM, 00186, Italy
Ospedale Sant'Andrea
Roma, RM, 00189, Italy
Università Campus Biomedico, Via Emilio Longoni, 83
Roma, Roma, 00155, Italy
A.O. S.Giovanni Calabita Fatebenefratelli
Roma, Roma, 00186, Italy
AULSS 18 di Rovigo
Rovigo, RO, 45100, Italy
Ospedale Morelli
Sondalo, SO, 23100, Italy
Università degli Studi
Candiolo, TO, 10060, Italy
Ospedale Mater Salutis
Legnago, VR, 37045, Italy
Istituto Tumori - Fondazione Pascale
Napoli, 80131, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 9, 2009
First Posted
December 10, 2009
Study Start
September 1, 2009
Primary Completion
April 1, 2015
Study Completion
June 1, 2015
Last Updated
July 15, 2015
Record last verified: 2009-12