Trial Comparing Two Two Sequences of Therapy in Colorectal Metastatic Patients

Metastatic Colorectal Cancer Clinical Trial

— COMETS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01030042
• Other study ID #: 2007-006254-26
• Status: Completed
• Phase: Phase 3
• First received: December 9, 2009
• Last updated: July 14, 2015
• Start date: September 2009
• Est. completion date: June 2015

Study information

• Verified date: December 2009
• Source: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: June 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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).
• 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.

Locations

Country	Name	City	State
Italy	A.O. Ospedale Umberto I - Università - Località Torretta	Ancona
Italy	Ospedali Riuniti, Largo Barozzi, 1	Bergamo
Italy	Fondazione Poliambulanza, Via Bissolati 57	Brescia
Italy	Spedali Civili	Brescia	BS
Italy	Università degli Studi	Candiolo	TO
Italy	Istituto Oncologico del Mediterraneo	Catania	CT
Italy	A.O. Ospedale S.Anna	Como
Italy	ASL 11	Empoli	FI
Italy	Ospedale Profili	Fabriano	AN
Italy	Usl 11 Ospedale Murri	Fermo	AP
Italy	Università	Firenze	FI
Italy	Ospedale Serbelloni	Gorgonzola	MI
Italy	AUSL di Lanciano-Vasto	Lanciano	CH
Italy	Ospedale Mater Salutis	Legnago	VR
Italy	Ospedale Maggiore	Lodi	LO
Italy	A.O. Carlo Poma - Via Albertoni, 1	Mantova
Italy	Istituto di Ricerca S.Raffaele	Milano	MI
Italy	Ospedale Fatebenefratelli	Milano	MI
Italy	A.O. S.Gerardo	Monza	MI
Italy	Istituto Tumori - Fondazione Pascale	Napoli
Italy	Istituto Oncologico Veneto	Padova	PD
Italy	A.O. S.Salvatore	Pesaro	PS
Italy	Azienda Ospedaliera San Carlo	Potenza	PZ
Italy	A.O. S.Giovanni Calabita Fatebenefratelli	Roma
Italy	Ospedale Sant'Andrea	Roma	RM
Italy	Università Campus Biomedico, Via Emilio Longoni, 83	Roma
Italy	Università Policlinico Umberto I	Roma	RM
Italy	AULSS 18 di Rovigo	Rovigo	RO
Italy	Ospedale Morelli	Sondalo	SO
Italy	Ospedale S.Vincenzo	Taormina	ME
Italy	A.O. Treviglio-Caravaggio, P.le Ospedale n1	Treviglio	Bergamo
Italy	Ospedale Civile	Urbino	PS

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		the time from the date of randomisation to the date of death	Yes
Secondary	Progression free survival		the time relapsed from the date of randomization and the date of progression after third-line treatment or death	Yes