FOLFOXIRI Compared With FOLFIRI for Metastatic Colorectal Cancer

Phase 3

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: FOLFIRI; Drug: FOLFOXIRI

• Registration Number: NCT01219920
• Lead Sponsor: Gruppo Oncologico del Nord-Ovest

Brief Summary

The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of response rate to conventional chemotherapy with the FOLFIRI regimen as first-line treatment of metastatic colorectal cancer patients.

Detailed Description

Survival of patients with metastatic colorectal cancer is correlated with the proportion of patients who receive all the three active drugs in the course of the disease, but not with the proportion of patients who receive any second-line therapy. In a sequential strategy, not all patients who progress after first-line chemotherapy are able to receive second-line treatment. Moreover, there is a correlation between the response rate to chemotherapy and the postchemotherapy radical resection rate of metastases.

Therefore, a way to improve the outcome of metastatic colorectal cancer patients could be to administer a first-line regimen containing the three active agents.

Study Timeline

• Study Start: 2001-11
• Primary Completion: 2005-11
• Study Completion: 2009-11
• Study First Submitted: 2010-10-08
• Study First Submitted QC: 2010-10-11
• Study First Posted: 2010-10-13
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-10
• Last Update Posted: 2015-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 244

Inclusion Criteria

• adenocarcinoma of the colon or rectum
• unresectable metastatic disease
• age 18 to 75 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower if age 70 years or younger or ECOG performance status of 0 if age 71 to 75 years measurable disease according to WHOcriteria
• leukocyte count of at least 3,500/mm3, neutrophils count of at least 1,500/mm3, platelet count of at least 100,000/mm3
• serum creatinine of 1.3 mg/dL or less
• serum bilirubin less than 1.5 mg/dL and AST, ALT, and alkaline phosphatase 2.5 x normal values or less (</= 5 if liver metastases)
• previous fluoropyrimidine-based adjuvant chemotherapy was allowed if ended more than 6 months before random assignment

Exclusion Criteria

• previous palliative chemotherapy for metastatic disease
• previous chemotherapy including irinotecan or oxaliplatin
• symptomatic cardiac disease, myocardial infarction in the last 24 months or uncontrolled arrhythmia
• active infections
• inflammatory bowel disease
• total colectomy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFIRI	FOLFIRI	Irinotecan 180 mg/sqm on day 1 Leucovorin 100 mg/sqm on day 1 and day 2 5-fluorouracil 400 mg/sqm bolus followed by 5-fluorouracil 600 mg/sqm 22-hour continuous infusion on day 1 and day 2 Repeated every 2 weeks
FOLFOXIRI	FOLFOXIRI	Irinotecan 165 mg/sqm on day 1 Oxaliplatin 85 mg/sqm on day 1 Leucovorin 200 mg/sqm on day 1 5-fluorouracil 3200 mg/sqm 48-hour continuous infusion starting on day 1 Repeated every 2 weeks

Primary Outcome Measures

Name	Time	Method
Response rate (RR)	Responses are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of treatment (6 months)	Responses are evaluated every 8 weeks according to WHO criteria. The determination of responses and progression was initially based on investigator-reported measurements; computed tomography scans of all responding patients and of patients with stable disease were subsequently subjected to external review by an independent panel.

Secondary Outcome Measures

Name	Time	Method
Postchemotherapy radical (R0) surgical resection rate of metastases	Postchemotherapy radical (R0) surgical resection rate of metastases were evaluated every 8 weeks during treatment and during follow up (36 months)	Percentage of patients who undergo radical (R0) resection of metastases after achieving objective response to chemotherapy.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Number of Participants with Adverse Events as a Measure of Safety and Tolerability were evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)	During the full lenght of first-line treatment, number of enrolled patients reporting adverse events is recorded. Adverse events are evaluated according to National Cancer Institute Common Toxicity Criteria version 2.0.
Progression-free survival (PFS)	Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months)	PFS is defined as the length of time from random assignment to disease progression or to death resulting from any cause, whichever occurred first, or to last contact.
Overall survival (OS)	For survival analysis participants are followed until death	OS is defined as the length of time from random assignment to death or to last contact.
Quality of life (QoL)	Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)	Quality of life is assessed at the beginning of each treatment cycle using the Quality of Life Questionnaire of the European Organisation for Research and Treatment of Cancer (version 2.0).; The QLQ-C30 questionnaire was analyzed with the global health status/quality-of-life scale as the primary end point and the other 10 scales as secondary end points.

Trial Locations

Locations (48)

A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica; 🇮🇹 Ancona, Italy

Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica; 🇮🇹 Alessandria, Italy

Ausl Della Valle D' Aosta (Ao) - Aosta (Ao) Oncologia Medica; 🇮🇹 Aosta, Italy

P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica; 🇮🇹 Arezzo, Italy

Azienda Ospedale 'G.Rummo' - Benevento (Bn) Oncologia Medica; 🇮🇹 Benevento, Italy

Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica; 🇮🇹 Brescia, Italy

Ospedale Versilia - Camaiore (Lu) Oncologia Medica; 🇮🇹 Camaiore, Italy

Ospedale Cecina - Cecina (Li) Oncologia Medica; 🇮🇹 Cecina, Italy

Asur - Zona Territoriale 6 Di Fabriano (An) - Fabriano (An) Oncologia Medica; 🇮🇹 Fabriano, Italy

Ausl 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica; 🇮🇹 Empoli, Italy

Ospedale Santa Croce Fano - Fano (Pu) Oncologia Medica; 🇮🇹 Fano, Italy

Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica; 🇮🇹 Firenze, Italy

A.O. Universitaria Careggi Di Firenze Oncologia Medica; 🇮🇹 Firenze, Italy

Irccs Istituto Nazionale Per La Ricerca Sul Cancro (Ist) - Genova (Ge) Oncologia Medica; 🇮🇹 Genova, Italy

Ospedale Sant'Andrea La Spezia - La Spezia (Sp) Oncologia Medica; 🇮🇹 La Spezia, Italy

E.O. Ospedali Galliera - Genova (Ge) Oncologia Medica; 🇮🇹 Genova, Italy

Ospedale Per Acuti "Mater Salutis" Legn. - Legnago (Vr) Oncologia Medica; 🇮🇹 Legnano, Italy

Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica; 🇮🇹 Lucca, Italy

A.O. Universitaria Federico Ii Di Napoli Oncologia Medica; 🇮🇹 Napoli, Italy

Ospedale Ca' Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica; 🇮🇹 Milano, Italy

Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica; 🇮🇹 Milano, Italy

A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica; 🇮🇹 Perugia, Italy

Ospedale Civile Di Mirano - Mirano (Ve) Oncologia Medica; 🇮🇹 Mirano, Italy

Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica; 🇮🇹 Pesaro, Italy

Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica; 🇮🇹 Pisa, Italy

A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica; 🇮🇹 Pisa, Italy

Ausl 3 Di Pistoia - Pistoia (Pt) Oncologia Medica; 🇮🇹 Pistoia, Italy

Ospedali Riuniti Di Pistoia - Pistoia (Pt) Oncologia Medica; 🇮🇹 Pistoia, Italy

Ospedale Di S. Maria Nuova - Reggio Nell'Emilia; 🇮🇹 Reggio Emilia, Italy

Policlinico Umberto I Di Roma Oncologia Medica; 🇮🇹 Roma, Italy

Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica; 🇮🇹 Roma, Italy

Ausl 7 Di Siena - Siena (Si) Oncologia Medica; 🇮🇹 Siena, Italy

A.O. Universitaria Senese Oncologia Medica; 🇮🇹 Siena, Italy

Ospedale Civile - Sondrio - Sondrio (So) Oncologia Medica; 🇮🇹 Sondrio, Italy

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Oncologia Medica; 🇮🇹 Torino, Italy

Ospedale Degli Infermi Di Biella - Biella (Bi) Oncologia Medica; 🇮🇹 Biella, Italy

Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica; 🇮🇹 Brindisi, Italy

Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica; 🇮🇹 Caltanissetta, Italy

Istituti Ospitalieri - Cremona - Cremona (Cr) Oncologia Medica; 🇮🇹 Cremona, Italy

Azienda Ospedaliera S. Croce E Carle Di Cuneo - Cuneo (Cn) Oncologia Medica; 🇮🇹 Cuneo, Italy

Ausl Le Di Lecce - Lecce (Le) Oncologia Chirurgica; 🇮🇹 Lecce, Italy

U.O. Oncologia Medica, Ospedale Civile; 🇮🇹 Livorno, Italy

A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica; 🇮🇹 Novara, Italy

A.O. Universitaria Di Parma Oncologia Medica; 🇮🇹 Parma, Italy

Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica; 🇮🇹 Perugia, Italy

Ospedale Piombino - Piombino (Li) Oncologia Medica; 🇮🇹 Piombino, Italy

A.O. Universitaria Pisana Oncologia Medica; 🇮🇹 Pisa, Italy

Policlinico Universitario Gemelli Di Roma Oncologia Medica; 🇮🇹 Roma, Italy