FOLFOXIRI Compared With FOLFIRI for Metastatic Colorectal Cancer

March 10, 2015 updated by: Gruppo Oncologico del 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 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

244

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • 5-FU
  • Campto
  • l-lederfolin
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:
  • Eloxatin
  • Campto
  • 5FU
  • l-leucovorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate (RR)
Time Frame: 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.
Responses are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of treatment (6 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 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.
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)
Time Frame: 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.
For survival analysis participants are followed until death
Postchemotherapy radical (R0) surgical resection rate of metastases
Time Frame: 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.
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
Time Frame: 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.
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)
Time Frame: 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.
Quality of life was evaluated every 2 weeks during treatment and every 8 weeks during follow up (36 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gruppo Oncologico del Nord-Ovest

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2001

Primary Completion (Actual)

November 1, 2005

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

October 8, 2010

First Submitted That Met QC Criteria

October 11, 2010

First Posted (Estimate)

October 13, 2010

Study Record Updates

Last Update Posted (Estimate)

March 11, 2015

Last Update Submitted That Met QC Criteria

March 10, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASL601LIOM03
  • 2007-002886-11 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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