Clinical trial NCT01219920: FOLFOXIRI Compared With FOLFIRI for Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic colorectal cancer
Phase III
FOLFOXIRI
FOLFIRI
Lead sponsor: Gruppo Oncologico del Nord-Ovest
Sponsor class: OTHER
First posted: 2010-10-13
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rate (RR)
timeFrame: Responses are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of treatment (6 months)
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months)
measure: Overall survival (OS)
timeFrame: For survival analysis participants are followed until death
measure: Postchemotherapy radical (R0) surgical resection rate of metastases
timeFrame: Postchemotherapy radical (R0) surgical resection rate of metastases were evaluated every 8 weeks during treatment and during follow up (36 months)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 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)
measure: Quality of life (QoL)
timeFrame: Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica
city: Ancona
country: Italy
facility: A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica
city: Aosta
country: Italy
facility: Ausl Della Valle D' Aosta (Ao) - Aosta (Ao) Oncologia Medica
city: Arezzo
country: Italy
facility: P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica
city: Benevento
country: Italy
facility: Azienda Ospedale 'G.Rummo' - Benevento (Bn) Oncologia Medica
city: Biella
country: Italy
facility: Ospedale Degli Infermi Di Biella - Biella (Bi) Oncologia Medica
city: Brescia
country: Italy
facility: Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica
city: Brindisi
country: Italy
facility: Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica
city: Caltanissetta
country: Italy
facility: Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica
city: Camaiore
country: Italy
facility: Ospedale Versilia - Camaiore (Lu) Oncologia Medica
city: Cecina
country: Italy
facility: Ospedale Cecina - Cecina (Li) Oncologia Medica
city: Cremona
country: Italy
facility: Istituti Ospitalieri - Cremona - Cremona (Cr) Oncologia Medica
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce E Carle Di Cuneo - Cuneo (Cn) Oncologia Medica
city: Empoli
country: Italy
facility: Ausl 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica
city: Fabriano
country: Italy
facility: Asur - Zona Territoriale 6 Di Fabriano (An) - Fabriano (An) Oncologia Medica
city: Fano
country: Italy
facility: Ospedale Santa Croce Fano - Fano (Pu) Oncologia Medica
city: Firenze
country: Italy
facility: Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica
city: Firenze
country: Italy
facility: A.O. Universitaria Careggi Di Firenze Oncologia Medica
city: Genova
country: Italy
facility: E.O. Ospedali Galliera - Genova (Ge) Oncologia Medica
city: Genova
country: Italy
facility: Irccs Istituto Nazionale Per La Ricerca Sul Cancro (Ist) - Genova (Ge) Oncologia Medica
city: La Spezia
country: Italy
facility: Ospedale Sant'Andrea La Spezia - La Spezia (Sp) Oncologia Medica
city: Lecce
country: Italy
facility: Ausl Le Di Lecce - Lecce (Le) Oncologia Chirurgica
city: Legnano
country: Italy
facility: Ospedale Per Acuti "Mater Salutis" Legn. - Legnago (Vr) Oncologia Medica
city: Livorno
country: Italy
facility: U.O. Oncologia Medica, Ospedale Civile
city: Lucca
country: Italy
facility: Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica
city: Milano
country: Italy
facility: Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica
city: Milano
country: Italy
facility: Ospedale Ca' Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica
city: Mirano
country: Italy
facility: Ospedale Civile Di Mirano - Mirano (Ve) Oncologia Medica
city: Napoli
country: Italy
facility: A.O. Universitaria Federico Ii Di Napoli Oncologia Medica
city: Novara
country: Italy
facility: A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica
city: Parma
country: Italy
facility: A.O. Universitaria Di Parma Oncologia Medica
city: Perugia
country: Italy
facility: Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica
city: Perugia
country: Italy
facility: A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica
city: Pesaro
country: Italy
facility: Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica
city: Piombino
country: Italy
facility: Ospedale Piombino - Piombino (Li) Oncologia Medica
city: Pisa
country: Italy
facility: Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica
city: Pisa
country: Italy
facility: A.O. Universitaria Pisana Oncologia Medica
city: Pistoia
country: Italy
facility: Ausl 3 Di Pistoia - Pistoia (Pt) Oncologia Medica
city: Pistoia
country: Italy
facility: Ospedali Riuniti Di Pistoia - Pistoia (Pt) Oncologia Medica
city: Reggio Emilia
country: Italy
facility: Ospedale Di S. Maria Nuova - Reggio Nell'Emilia
city: Roma
country: Italy
facility: Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica
city: Roma
country: Italy
facility: Policlinico Umberto I Di Roma Oncologia Medica
city: Roma
country: Italy
facility: Policlinico Universitario Gemelli Di Roma Oncologia Medica
city: Siena
country: Italy
facility: A.O. Universitaria Senese Oncologia Medica
city: Siena
country: Italy
facility: Ausl 7 Di Siena - Siena (Si) Oncologia Medica
city: Sondrio
country: Italy
facility: Ospedale Civile - Sondrio - Sondrio (So) Oncologia Medica
city: Torino
country: Italy
facility: A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Oncologia Medica
Study officials:
affiliation: University of Pisa
name: Alfredo Falcone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino 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. doi: 10.1200/JCO.2006.09.0928.
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.
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.
citation: Cremolini C, Loupakis F, Masi G, Lonardi S, Granetto C, Mancini ML, Chiara S, Moretto R, Rossini D, Vitello S, Allegrini G, Tonini G, Bergamo F, Tomasello G, Ronzoni M, Buonadonna A, Bustreo S, Barbara C, Boni L, Falcone A. FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials. Ann Oncol. 2016 May;27(5):843-9. doi: 10.1093/annonc/mdw052. Epub 2016 Feb 9.