FOLFOXIRI Compared With FOLFIRI for Metastatic Colorectal Cancer

• Sponsor: Gruppo Oncologico del Nord-Ovest (Other)
• Overall Status: Completed
• CT.gov ID: NCT01219920
• Collaborator: (none)
• Enrollment: 244
• Locations: 48
• Arms: 2
• Duration (Months): 96
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: FOLFIRI; Drug: FOLFOXIRI	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 244 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Nov 1, 2001
• Actual Primary Completion Date: Nov 1, 2005
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	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; Other Names: Campto l-lederfolin 5-FU
Experimental: 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	Drug: 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; Other Names: Campto Eloxatin l-leucovorin 5FU

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al) Oncologia Medica	Alessandria		Italy	15100
2	A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona - Ancona (An) Oncologia Medica	Ancona		Italy	60100
3	Ausl Della Valle D' Aosta (Ao) - Aosta (Ao) Oncologia Medica	Aosta		Italy	11100
4	P.O. Zona Aretina - Ospedale S. Donato Di Arezzo - Arezzo (Ar) Oncologia Medica	Arezzo		Italy	52100
5	Azienda Ospedale 'G.Rummo' - Benevento (Bn) Oncologia Medica	Benevento		Italy	82100
6	Ospedale Degli Infermi Di Biella - Biella (Bi) Oncologia Medica	Biella		Italy	13900
7	Ospedale S. Orsola F.B.F. - Brescia - Brescia (Bs) Oncologia Medica	Brescia		Italy	25122
8	Stabilimento "Perrino" - Brindisi - Brindisi (Br) Oncologia Medica	Brindisi		Italy	72100
9	Azienda Ospedaliera S. Elia - Caltanissetta (Cl) Oncologia Medica	Caltanissetta		Italy	93100
10	Ospedale Versilia - Camaiore (Lu) Oncologia Medica	Camaiore		Italy	55043
11	Ospedale Cecina - Cecina (Li) Oncologia Medica	Cecina		Italy	57023
12	Istituti Ospitalieri - Cremona - Cremona (Cr) Oncologia Medica	Cremona		Italy	26100
13	Azienda Ospedaliera S. Croce E Carle Di Cuneo - Cuneo (Cn) Oncologia Medica	Cuneo		Italy	12100
14	Ausl 11 Di Empoli (Fi) - Empoli (Fi) Oncologia Medica	Empoli		Italy	50053
15	Asur - Zona Territoriale 6 Di Fabriano (An) - Fabriano (An) Oncologia Medica	Fabriano		Italy	60044
16	Ospedale Santa Croce Fano - Fano (Pu) Oncologia Medica	Fano		Italy	61032
17	Ausl 10 Di Firenze - Firenze (Fi) Oncologia Medica	Firenze		Italy	50122
18	A.O. Universitaria Careggi Di Firenze Oncologia Medica	Firenze		Italy	50134
19	E.O. Ospedali Galliera - Genova (Ge) Oncologia Medica	Genova		Italy	16128
20	Irccs Istituto Nazionale Per La Ricerca Sul Cancro (Ist) - Genova (Ge) Oncologia Medica	Genova		Italy	16132
21	Ospedale Sant'Andrea La Spezia - La Spezia (Sp) Oncologia Medica	La Spezia		Italy	19100
22	Ausl Le Di Lecce - Lecce (Le) Oncologia Chirurgica	Lecce		Italy	73100
23	Ospedale Per Acuti "Mater Salutis" Legn. - Legnago (Vr) Oncologia Medica	Legnano		Italy	37045
24	U.O. Oncologia Medica, Ospedale Civile	Livorno		Italy	57123
25	Presidio Ospedaliero Piana Di Lucca - Lucca (Lu) Oncologia Medica	Lucca		Italy	55100
26	Irccs Fondazione Centro S. Raffaele Del Monte Tabor - Milano (Mi) Oncologia Medica	Milano		Italy	20132
27	Ospedale Ca' Granda-Niguarda - Milano - Milano (Mi) Oncologia Medica	Milano		Italy	20162
28	Ospedale Civile Di Mirano - Mirano (Ve) Oncologia Medica	Mirano		Italy	30035
29	A.O. Universitaria Federico Ii Di Napoli Oncologia Medica	Napoli		Italy	80131
30	A.O. Universitaria Maggiore Della Carita' Di Novara Oncologia Medica	Novara		Italy	28100
31	A.O. Universitaria Di Parma Oncologia Medica	Parma		Italy	43100
32	Asl 1 Di Citta' Di Castello (Pg) - Citta' Di Castello (Pg) Oncologia Medica	Perugia		Italy	06012
33	A.O. Di Perugia - Ospedale S. Maria Della Misericordia (Ex Silvestrini) - Perugia (Pg) Oncologia Medica	Perugia		Italy	06156
34	Azienda Ospedaliera San Salvatore - Pesaro (Pu) Oncologia Medica	Pesaro		Italy	61100
35	Ospedale Piombino - Piombino (Li) Oncologia Medica	Piombino		Italy	57025
36	Ausl 5 Di Pisa - Pisa (Pi) Oncologia Medica	Pisa		Italy	56100
37	A.O. Universitaria Pisana - Pisa (Pi) Oncologia Medica	Pisa		Italy	56126
38	A.O. Universitaria Pisana Oncologia Medica	Pisa		Italy	56126
39	Ausl 3 Di Pistoia - Pistoia (Pt) Oncologia Medica	Pistoia		Italy	51100
40	Ospedali Riuniti Di Pistoia - Pistoia (Pt) Oncologia Medica	Pistoia		Italy	51100
41	Ospedale Di S. Maria Nuova - Reggio Nell'Emilia	Reggio Emilia		Italy	42100
42	Policlinico Universitario Campus Bio-Medico Di Roma Oncologia Medica	Roma		Italy	00128
43	Policlinico Umberto I Di Roma Oncologia Medica	Roma		Italy	00161
44	Policlinico Universitario Gemelli Di Roma Oncologia Medica	Roma		Italy	00168
45	A.O. Universitaria Senese Oncologia Medica	Siena		Italy	53100
46	Ausl 7 Di Siena - Siena (Si) Oncologia Medica	Siena		Italy	53100
47	Ospedale Civile - Sondrio - Sondrio (So) Oncologia Medica	Sondrio		Italy	23100
48	A.O. Universitaria S. Giovanni Battista-Molinette Di Torino Oncologia Medica	Torino		Italy	10134

Sponsors and Collaborators

• Gruppo Oncologico del Nord-Ovest

Investigators

• Principal Investigator: Alfredo Falcone, MD, University of Pisa

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.

• Responsible Party: Gruppo Oncologico del Nord-Ovest
• ClinicalTrials.gov Identifier: NCT01219920
• Other Study ID Numbers: ASL601LIOM03; 2007-002886-11
• First Posted: Oct 13, 2010
• Last Update Posted: Mar 11, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Gruppo Oncologico del Nord-Ovest: Metastatic colorectal cancer; Phase III; FOLFOXIRI; FOLFIRI
• Additional relevant MeSH terms: Colorectal Neoplasms; Leucovorin; Irinotecan

Study Results

No Results Posted as of Mar 11, 2015