FOLFOXIRI Compared With FOLFIRI for Metastatic Colorectal Cancer

NCT01219920 | Completed Phase 3 DMC

• 2 other identifiers: ASL601LIOM032007-002886-11
• Study Type: interventional
• Target: 244
• Locations: 1 country
• Sites: 48

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic colorectal cancer; Phase III; FOLFOXIRI; FOLFIRI

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• 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)

• Overall survival (OS)

  For survival analysis participants are followed until death

• 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)

• 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)

• Quality of life (QoL)

  Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)

Study Arms (2)

FOLFIRI

ACTIVE COMPARATOR

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

Drug: FOLFIRI

FOLFOXIRI

EXPERIMENTAL

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

Drug: FOLFOXIRI

Interventions

FOLFIRI DRUG

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

Also known as: Campto, l-lederfolin, 5-FU

FOLFIRI

FOLFOXIRI DRUG

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

Also known as: Campto, Eloxatin, l-leucovorin, 5FU

FOLFOXIRI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (48)

Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica

Alessandria, 15100, Italy

Location

A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica

Ancona, 60100, Italy

Location

Ausl Della Valle D' Aosta (Ao) - Aosta (Ao) Oncologia Medica

Aosta, 11100, Italy

Location

P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica

Arezzo, 52100, Italy

Location

Azienda Ospedale 'G.Rummo' - Benevento (Bn) Oncologia Medica

Benevento, 82100, Italy

Location

Ospedale Degli Infermi Di Biella - Biella (Bi) Oncologia Medica

Biella, 13900, Italy

Location

Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica

Brescia, 25122, Italy

Location

Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica

Brindisi, 72100, Italy

Location

Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica

Caltanissetta, 93100, Italy

Location

Ospedale Versilia - Camaiore (Lu) Oncologia Medica

Camaiore, 55043, Italy

Location

Ospedale Cecina - Cecina (Li) Oncologia Medica

Cecina, 57023, Italy

Location

Istituti Ospitalieri - Cremona - Cremona (Cr) Oncologia Medica

Cremona, 26100, Italy

Location

Azienda Ospedaliera S. Croce E Carle Di Cuneo - Cuneo (Cn) Oncologia Medica

Cuneo, 12100, Italy

Location

Ausl 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica

Empoli, 50053, Italy

Location

Asur - Zona Territoriale 6 Di Fabriano (An) - Fabriano (An) Oncologia Medica

Fabriano, 60044, Italy

Location

Ospedale Santa Croce Fano - Fano (Pu) Oncologia Medica

Fano, 61032, Italy

Location

Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica

Florence, 50122, Italy

Location

A.O. Universitaria Careggi Di Firenze Oncologia Medica

Florence, 50134, Italy

Location

E.O. Ospedali Galliera - Genova (Ge) Oncologia Medica

Genova, 16128, Italy

Location

Irccs Istituto Nazionale Per La Ricerca Sul Cancro (Ist) - Genova (Ge) Oncologia Medica

Genova, 16132, Italy

Location

Ospedale Sant'Andrea La Spezia - La Spezia (Sp) Oncologia Medica

La Spezia, 19100, Italy

Location

Ausl Le Di Lecce - Lecce (Le) Oncologia Chirurgica

Lecce, 73100, Italy

Location

Ospedale Per Acuti "Mater Salutis" Legn. - Legnago (Vr) Oncologia Medica

Legnano, 37045, Italy

Location

U.O. Oncologia Medica, Ospedale Civile

Livorno, 57123, Italy

Location

Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica

Lucca, 55100, Italy

Location

Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica

Milan, 20132, Italy

Location

Ospedale Ca' Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica

Milan, 20162, Italy

Location

Ospedale Civile Di Mirano - Mirano (Ve) Oncologia Medica

Mirano, 30035, Italy

Location

A.O. Universitaria Federico Ii Di Napoli Oncologia Medica

Napoli, 80131, Italy

Location

A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica

Novara, 28100, Italy

Location

A.O. Universitaria Di Parma Oncologia Medica

Parma, 43100, Italy

Location

Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica

Perugia, 06012, Italy

Location

A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica

Perugia, 06156, Italy

Location

Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica

Pesaro, 61100, Italy

Location

Ospedale Piombino - Piombino (Li) Oncologia Medica

Piombino, 57025, Italy

Location

Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica

Pisa, 56100, Italy

Location

A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica

Pisa, 56126, Italy

Location

A.O. Universitaria Pisana Oncologia Medica

Pisa, 56126, Italy

Location

Ausl 3 Di Pistoia - Pistoia (Pt) Oncologia Medica

Pistoia, 51100, Italy

Location

Ospedali Riuniti Di Pistoia - Pistoia (Pt) Oncologia Medica

Pistoia, 51100, Italy

Location

Ospedale Di S. Maria Nuova - Reggio Nell'Emilia

Reggio Emilia, 42100, Italy

Location

Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica

Roma, 00128, Italy

Location

Policlinico Umberto I Di Roma Oncologia Medica

Roma, 00161, Italy

Location

Policlinico Universitario Gemelli Di Roma Oncologia Medica

Roma, 00168, Italy

Location

A.O. Universitaria Senese Oncologia Medica

Siena, 53100, Italy

Location

Ausl 7 Di Siena - Siena (Si) Oncologia Medica

Siena, 53100, Italy

Location

Ospedale Civile - Sondrio - Sondrio (So) Oncologia Medica

Sondrio, 23100, Italy

Location

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Oncologia Medica

Torino, 10134, Italy

Location

Related Publications (4)

• 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.

  PMID: 17470860 BACKGROUND

• 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.

  PMID: 18279572 BACKGROUND

• 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.

  PMID: 19247029 BACKGROUND

• 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.

  PMID: 26861604 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

IFL protocol; Irinotecan; Fluorouracil; FOLFOXIRI protocol; Oxaliplatin; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Alfredo Falcone, MD

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 13, 2010
• Study Start: November 1, 2001
• Primary Completion: November 1, 2005
• Study Completion: November 1, 2009
• Last Updated: March 11, 2015

Record last verified: 2015-03

Locations

IT (48)