FOLFOXIRI Compared With FOLFIRI for Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

Official title:

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) as First-line Treatment for Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01219920
• Other study ID #: ASL601LIOM03
• Secondary ID: 2007-002886-11
• Status: Completed
• Phase: Phase 3
• First received: October 8, 2010
• Last updated: March 10, 2015
• Start date: November 2001
• Est. completion date: November 2009

Study information

• Verified date: March 2015
• Source: Gruppo Oncologico del Nord-Ovest
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: November 2009
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• 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
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

Locations

Country	Name	City	State
Italy	Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica	Alessandria
Italy	A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica	Ancona
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 Degli Infermi Di Biella - Biella (Bi) Oncologia Medica	Biella
Italy	Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica	Brescia
Italy	Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica	Brindisi
Italy	Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica	Caltanissetta
Italy	Ospedale Versilia - Camaiore (Lu) Oncologia Medica	Camaiore
Italy	Ospedale Cecina - Cecina (Li) Oncologia Medica	Cecina
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 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica	Empoli
Italy	Asur - Zona Territoriale 6 Di Fabriano (An) - Fabriano (An) Oncologia Medica	Fabriano
Italy	Ospedale Santa Croce Fano - Fano (Pu) Oncologia Medica	Fano
Italy	A.O. Universitaria Careggi Di Firenze Oncologia Medica	Firenze
Italy	Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica	Firenze
Italy	E.O. Ospedali Galliera - Genova (Ge) Oncologia Medica	Genova
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	Ausl Le Di Lecce - Lecce (Le) Oncologia Chirurgica	Lecce
Italy	Ospedale Per Acuti "Mater Salutis" Legn. - Legnago (Vr) Oncologia Medica	Legnano
Italy	U.O. Oncologia Medica, Ospedale Civile	Livorno
Italy	Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica	Lucca
Italy	Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica	Milano
Italy	Ospedale Ca` Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica	Milano
Italy	Ospedale Civile Di Mirano - Mirano (Ve) Oncologia Medica	Mirano
Italy	A.O. Universitaria Federico Ii Di Napoli Oncologia Medica	Napoli
Italy	A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica	Novara
Italy	A.O. Universitaria Di Parma Oncologia Medica	Parma
Italy	A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica	Perugia
Italy	Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica	Perugia
Italy	Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica	Pesaro
Italy	Ospedale Piombino - Piombino (Li) Oncologia Medica	Piombino
Italy	A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica	Pisa
Italy	A.O. Universitaria Pisana Oncologia Medica	Pisa
Italy	Ausl 5 Di Pisa - 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	Policlinico Universitario Gemelli Di Roma Oncologia Medica	Roma
Italy	A.O. Universitaria Senese Oncologia Medica	Siena
Italy	Ausl 7 Di Siena - Siena (Si) 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

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Oncologico del Nord-Ovest

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinò L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. — View Citation

Masi G, Loupakis F, Pollina L, Vasile E, Cupini S, Ricci S, Brunetti IM, Ferraldeschi R, Naso G, Filipponi F, Pietrabissa A, Goletti O, Baldi G, Fornaro L, Andreuccetti M, Falcone A. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg. 2009 Mar;249(3):420-5. doi: 10.1097/SLA.0b013e31819a0486. — View Citation

Masi G, Vasile E, Loupakis F, Bursi S, Ricci S, Petrini I, Fontana A, Allegrini G, Falcone A. Triplet combination of fluoropyrimidines, oxaliplatin, and irinotecan in the first-line treatment of metastatic colorectal cancer. Clin Colorectal Cancer. 2008 Jan;7(1):7-14. doi: 10.3816/CCC.2008.n.002. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (RR)	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.	Responses are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of treatment (6 months)	No
Secondary	Progression-free survival (PFS)	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.	Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months)	No
Secondary	Overall survival (OS)	OS is defined as the length of time from random assignment to death or to last contact.	For survival analysis participants are followed until death	No
Secondary	Postchemotherapy radical (R0) surgical resection rate of metastases	Percentage of patients who undergo radical (R0) resection of metastases after achieving objective response to chemotherapy.	Postchemotherapy radical (R0) surgical resection rate of metastases were evaluated every 8 weeks during treatment and during follow up (36 months)	No
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	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.	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)	Yes
Secondary	Quality of life (QoL)	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.	Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)	Yes