Trial Comparing Two Two Sequences of Therapy in Colorectal Metastatic Patients (COMETS)
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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 |
- Overall Survival [ Time Frame: the time from the date of randomisation to the date of death ] [ Designated as safety issue: Yes ]
- 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: | March 2014 |
| Estimated Primary Completion Date: | September 2012 (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 |
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| Contact: Roberto Labianca, MD | +39 035 269 ext 859 | rlabian@tin.it |
| Contact: Silvia Rota, DM | +39 0331 490052 | centrotrialgiscad@yahoo.it |
| 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 | |
| Ospedale Fatebenefratelli | Active, not recruiting |
| Milano, MI, Italy, 20100 | |
| Istituto di Ricerca S.Raffaele | 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 | |
More Information
No publications provided
| Responsible Party: | Roberto Labianca as President of GISCAD, GISCAD |
| ClinicalTrials.gov Identifier: | NCT01030042 History of Changes |
| Other Study ID Numbers: | 2007-006254-26 |
| Study First Received: | December 9, 2009 |
| Last Updated: | December 9, 2009 |
| 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 May 21, 2013