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Trial Comparing Two Two Sequences of Therapy in Colorectal Metastatic Patients (COMETS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01030042
Recruitment Status : Completed
First Posted : December 10, 2009
Last Update Posted : July 15, 2015
Information provided by (Responsible Party):
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: FOLFOX-4 Drug: Irinotecan/Cetuximab Phase 3

Detailed Description:

Target population:

Patients with histologically confirmed metastatic colorectal cancer progressed after a first line treatment containing FOLFIRI and BEV

Inclusion criteria:

  • Age >18 < 75 years of age
  • Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
  • K-ras wild-type
  • ECOG performance status 0-1 at study entry


- Response Rate, Disease control rate, The duration of overall response, Overall survival, PFS, Time to treatment failure, Quality of Life, Incidence of AEs, Frequency and nature of serious adverse reactions (SADRs), Premature withdrawals

Statistical methods:

Assuming a randomization ratio of 1:1, 282 deaths are required in order to achieve a power of 80% of detecting a hazard ratio of 0.72 in favour of one of the two sequences, translating in an increase of median survival time from 10 to 14 months, with a type I error of 5%, two-sided, using the Mantel-Cox version of the log-rank test. With a uniform accrual period of 3 years and a follow-up of 18 months, about 350 patients will be needed to reach the target number of events.

All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will be applied to describe study flow and protocol deviations.

All OS and PFS curves will be drawn with the Kaplan-Meier method. Results will be presented as Hazard Ratio (HRs) and their 95% Confidence Interval (CIs).

On annual basis, starting from the second year, an interim analysis will be conducted. In principle, no formal stopping rule will be applied, unless otherwise suggested by the DSMC. Safety reports will be drawn on annual basis.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2009
Actual Primary Completion Date : April 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Cetuximab/Irinotecan
Cetuximab/irinotecan followed, after progression, by FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil)
Drug: Irinotecan/Cetuximab

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.

Other Name: CPT11/Cetuximab

Active Comparator: FOLFOX 4
FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil) followed, after progression, by irinotecan/cetuximab
Drug: FOLFOX-4
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).
Other Name: Oxaliplatin, 5FU, Leucovorin

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: the time from the date of randomisation to the date of death ]

Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: the time relapsed from the date of randomization and the date of progression after third-line treatment or death ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01030042

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Ospedale Profili
Fabriano, AN, Italy, 60044
Usl 11 Ospedale Murri
Fermo, AP, Italy, 63023
A.O. Treviglio-Caravaggio, P.le Ospedale n1
Treviglio, Bergamo, Italy, 24047
Spedali Civili
Brescia, BS, Italy, 25100
AUSL di Lanciano-Vasto
Lanciano, CH, Italy, 66034
Istituto Oncologico del Mediterraneo
Catania, CT, Italy, 95029
ASL 11
Empoli, FI, Italy, 50010
Firenze, FI, Italy, 50139
Ospedale Maggiore
Lodi, LO, Italy, 26900
Ospedale S.Vincenzo
Taormina, ME, Italy, 98039
Ospedale Serbelloni
Gorgonzola, MI, Italy, 20064
Istituto di Ricerca S.Raffaele
Milano, MI, Italy, 20100
Ospedale Fatebenefratelli
Milano, MI, Italy, 20100
A.O. S.Gerardo
Monza, MI, Italy, 20052
Istituto Oncologico Veneto
Padova, PD, Italy, 35124
A.O. S.Salvatore
Pesaro, PS, Italy, 61100
Ospedale Civile
Urbino, PS, Italy, 61029
Azienda Ospedaliera San Carlo
Potenza, PZ, Italy, 85100
Università Policlinico Umberto I
Roma, RM, Italy, 00186
Ospedale Sant'Andrea
Roma, RM, Italy, 00189
AULSS 18 di Rovigo
Rovigo, RO, Italy, 45100
Ospedale Morelli
Sondalo, SO, Italy, 23100
Università degli Studi
Candiolo, TO, Italy, 10060
Ospedale Mater Salutis
Legnago, VR, Italy, 37045
A.O. Ospedale Umberto I - Università - Località Torretta
Ancona, Italy, 60020
Ospedali Riuniti, Largo Barozzi, 1
Bergamo, Italy, 24128
Fondazione Poliambulanza, Via Bissolati 57
Brescia, Italy, 25100
A.O. Ospedale S.Anna
Como, Italy, 22100
A.O. Carlo Poma - Via Albertoni, 1
Mantova, Italy, 46100
Istituto Tumori - Fondazione Pascale
Napoli, Italy, 80131
Università Campus Biomedico, Via Emilio Longoni, 83
Roma, Italy, 00155
A.O. S.Giovanni Calabita Fatebenefratelli
Roma, Italy, 00186
Sponsors and Collaborators
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

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Responsible Party: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente Identifier: NCT01030042     History of Changes
Other Study ID Numbers: 2007-006254-26
First Posted: December 10, 2009    Key Record Dates
Last Update Posted: July 15, 2015
Last Verified: December 2009
Keywords provided by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente:
colorectal cancer
two sequences therapy
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological