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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2009 by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
ClinicalTrials.gov Identifier:
NCT01030042
First received: December 9, 2009
Last updated: November 6, 2013
Last verified: December 2009
  Purpose

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 Intervention Phase
Metastatic Colorectal Cancer
Drug: FOLFOX-4
Drug: Irinotecan/Cetuximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label Randomized, Parallel Group, Phase III, Multicenter Trial Comparing Two Different Sequences of Therapy (Irinotecan/Cetuximab Followed by Fluorouracil/Leucovorin With Oxaliplatin (FOLFOX-4) vs FOLFOX-4 Followed by Irinotecan/Cetuximab) in Metastatic Colorectal Patients Treated With Fluorouracil/Leucovorin With Irinotecan FOLFIRI /Bevacizumab as First Line Chemotherapy

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: the time from the date of randomisation to the date of death ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: the time relapsed from the date of randomization and the date of progression after third-line treatment or death ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 350
Study Start Date: September 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab/Irinotecan 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.

Active Comparator: B
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).

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

Endpoints:

- 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01030042

Contacts
Contact: Roberto Labianca, MD +39 035 269 ext 859 rlabian@tin.it
Contact: Silvia Rota, DM +39 0331 490052 centrotrialgiscad@yahoo.it

Locations
Italy
Ospedale Profili Active, not recruiting
Fabriano, AN, Italy, 60044
Usl 11 Ospedale Murri Not yet recruiting
Fermo, AP, Italy, 63023
Principal Investigator: Lucio Giustini, MD         
A.O. Treviglio-Caravaggio, P.le Ospedale n1 Active, not recruiting
Treviglio, Bergamo, Italy, 24047
Spedali Civili Active, not recruiting
Brescia, BS, Italy, 25100
AUSL di Lanciano-Vasto Active, not recruiting
Lanciano, CH, Italy, 66034
Istituto Oncologico del Mediterraneo Active, not recruiting
Catania, CT, Italy, 95029
ASL 11 Not yet recruiting
Empoli, FI, Italy, 50010
Principal Investigator: Gianmaria Fiorentini, MD         
Università Not yet recruiting
Firenze, FI, Italy, 50139
Principal Investigator: Enrico Mini, MD         
Ospedale Maggiore Not yet recruiting
Lodi, LO, Italy, 26900
Principal Investigator: Giovanni Ucci, MD         
Ospedale S.Vincenzo Active, not recruiting
Taormina, ME, Italy, 98039
Ospedale Serbelloni Recruiting
Gorgonzola, MI, Italy, 20064
Principal Investigator: Luciano Isa, MD         
Istituto di Ricerca S.Raffaele Active, not recruiting
Milano, MI, Italy, 20100
Ospedale Fatebenefratelli Active, not recruiting
Milano, MI, Italy, 20100
A.O. S.Gerardo Active, not recruiting
Monza, MI, Italy, 20052
Istituto Oncologico Veneto Active, not recruiting
Padova, PD, Italy, 35124
A.O. S.Salvatore Active, not recruiting
Pesaro, PS, Italy, 61100
Ospedale Civile Not yet recruiting
Urbino, PS, Italy, 61029
Principal Investigator: Enrico Testa, MD         
Azienda Ospedaliera San Carlo Active, not recruiting
Potenza, PZ, Italy, 85100
Università Policlinico Umberto I Not yet recruiting
Roma, RM, Italy, 00186
Principal Investigator: Enrico Cortesi, MD         
Ospedale Sant'Andrea Recruiting
Roma, RM, Italy, 00189
Principal Investigator: Andrea Marchetti, MD         
AULSS 18 di Rovigo Active, not recruiting
Rovigo, RO, Italy, 45100
Ospedale Morelli Active, not recruiting
Sondalo, SO, Italy, 23100
Università degli Studi Active, not recruiting
Candiolo, TO, Italy, 10060
Ospedale Mater Salutis Not yet recruiting
Legnago, VR, Italy, 37045
Principal Investigator: Andrea Bonetti, MD         
A.O. Ospedale Umberto I - Università - Località Torretta Active, not recruiting
Ancona, Italy, 60020
Ospedali Riuniti, Largo Barozzi, 1 Active, not recruiting
Bergamo, Italy, 24128
Fondazione Poliambulanza, Via Bissolati 57 Active, not recruiting
Brescia, Italy, 25100
A.O. Ospedale S.Anna Active, not recruiting
Como, Italy, 22100
A.O. Carlo Poma - Via Albertoni, 1 Active, not recruiting
Mantova, Italy, 46100
Istituto Tumori - Fondazione Pascale Recruiting
Napoli, Italy, 80131
Principal Investigator: Giuseppe Nasti, MD         
A.O. S.Giovanni Calabita Fatebenefratelli Not yet recruiting
Roma, Italy, 00186
Principal Investigator: Domenico Corsi, MD         
Università Campus Biomedico, Via Emilio Longoni, 83 Not yet recruiting
Roma, Italy, 00155
Principal Investigator: Giuseppe Tonini, MPr         
Sponsors and Collaborators
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
  More Information

No publications provided

Responsible Party: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
ClinicalTrials.gov Identifier: NCT01030042     History of Changes
Other Study ID Numbers: 2007-006254-26
Study First Received: December 9, 2009
Last Updated: November 6, 2013
Health Authority: Italy: Ethics Committee
Italy: The Italian Medicines Agency

Keywords provided by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente:
metastatic
colorectal cancer
two sequences therapy
metastatic colorectal cancer patients progressed after a I line treatment containing FOLFIRI and BEV

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Irinotecan
Cetuximab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on August 26, 2014