FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer (TOSCA)

November 25, 2014 updated by: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

A Randomized Trial Investigating the Role of FOLFOX-4 Regimen Duration (3 Versus 6 Months) and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer

This project consists of two independent, following specific eligibility criteria and different randomisation schemes studies, later on called DURATION study and BEV study. Once randomised in the duration study, patients fulfilling eligibility criteria for BEV study may also be randomized to receive BEV or no BEV, in addition to FOLFOX-4 chemotherapy.

As both are open label studies, there will be no blinding of treatment assignment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

At the present time the standard treatment for resected colon cancer with high possibility of relapse ("high risk" stage II and all stage III) is represented by the regimen FOLFOX (leucovorin, bolus and infusional 5fluorouracil and oxaliplatin), which is able to increase significantly the disease-free survival (DFS) at 3 and 4 years, whereas the advantage for 5-year overall survival (OS) (which is predicted by the previous parameter) could be observed only with a further increase of follow-up. The conventional duration of chemotherapy is today of 6 months (12 courses every 2 weeks), but this long drug exposure increases the risk of long-term neurotoxicity. A reduction of adjuvant chemotherapy under 6 months was proven effective in other cancers (breast, testis…) and is better tolerated by patients in clinical practice. On the other hand, bevacizumab significantly increases OS and all other parameters when combined with standard chemotherapy in advanced disease.

Study Type

Interventional

Enrollment (Actual)

3756

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
      • Bergamo, Italy, 24128
        • Ospedali Riuniti, Largo Barozzi, 1
      • Castellamare di Stabbia, Italy, 80053
        • Ospedale S.Leonardo
      • Firenze, Italy, 50139
        • A.O. Careggi-Università, Viale Pieraccini, 17
      • Napoli, Italy, 80131
        • A.O. Cardarelli
      • Napoli, Italy, 80130
        • Fondazione Pascale - Istituto Tumori
      • Napoli, Italy, 80130
        • Istituto Tumori- Pascale
      • Napoli, Italy, 80130
        • Università Federico II
      • Napoli, Italy, 80131
        • Azienda Ospedaliera
      • Napoli, Italy, 80131
        • Ospedale S.Gennaro
      • Novara, Italy, 28100
        • A.O. Ospedale Maggiore della carità
      • Roma, Italy, 00155
        • Università Campus Biomedico, Via Emilio Longoni, 83
      • Roma, Italy, 00186
        • A.O. S.Giovanni Calabita Fatebenefratelli
    • AL
      • Casale Monferrato, AL, Italy, 15033
        • Ospedale Santo Spirito
    • AN
      • Ancona, AN, Italy, 62020
        • A.O. Umberto I -Università Località Torrette
      • Fabriano, AN, Italy, 60044
        • Ospedale Profili
    • AP
      • Ascoli Piceno, AP, Italy, 63100
        • Ospedale Mazzoni
      • Fermo, AP, Italy, 63023
        • Usl 11 Ospedale Murri
    • AQ
      • L'Aquila, AQ, Italy, 67100
        • Università di L'Aquila
    • AR
      • Arezzo, AR, Italy, 52100
        • ASL 8 di Arezzo
      • Montevarchi, AR, Italy, 52025
        • P.O. Ospedale S.M. Della Gruccia
    • AT
      • Asti, AT, Italy, 14100
        • Ospedale Civile
    • BA
      • Altamura, BA, Italy, 70100
        • Ospedale di Altamura
    • BI
      • Biella, BI, Italy, 13900
        • Ospedale Degli Infermi
    • BN
      • Benevento, BN, Italy, 82100
        • A.O. G.Rummo
    • BS
      • Brescia, BS, Italy, 15100
        • Fondazione Poliambulanza
      • Brescia, BS, Italy, 15100
        • Ospedale S.Orsola Fatebenefratelli
      • Brescia, BS, Italy, 25100
        • Spedali Civili
      • Iseo, BS, Italy, 25049
        • Azienda M.Mellini-Chiara
    • BZ
      • Bolzano, BZ, Italy, 39100
        • Ospedale Regionale
    • Bergamo
      • Treviglio, Bergamo, Italy, 24047
        • A.O. Treviglio-Caravaggio, P.le Ospedale n1
    • Bs
      • Manerbio, Bs, Italy, 25025
        • Ospedale di Manerbio
    • CA
      • Iglesias, CA, Italy, 09016
        • Ospedale S.Barbara - Asl 7
      • Monserrato, CA, Italy, 09042
        • Policlinico Universitario
    • CE
      • Caserta, CE, Italy, 81100
        • A.O. S.Sebastiano
    • CH
      • Lanciano, CH, Italy, 66034
        • AUSL di Lanciano-Vasto
    • CN
      • Alba, CN, Italy, 12051
        • Ospedale S.Lazzaro
      • Cuneo, CN, Italy, 12100
        • A.O. S.Croce e Carle
    • CO
      • Como, CO, Italy, 22100
        • Ospedale S.Anna
      • Como, CO, Italy, 22100
        • Ospedale Valduce
      • Erba, CO, Italy, 22036
        • Ospedale Fatebenefratelli Sacra Famiglia
    • CR
      • Cremona, CR, Italy, 26100
        • Azienda Istituti Ospitalieri
    • CT
      • Catania, CT, Italy, 95100
        • Azienda Ospedaliera
    • CZ
      • Lamezia Terme, CZ, Italy, 88046
        • ASL 6 - Ospedale Civile
    • FI
      • Empoli, FI, Italy, 50010
        • ASL 11
      • Firenze, FI, Italy, 50011
        • Ospedale S.M.Annunziata-ASL FI
      • Firenze, FI, Italy, 50100
        • A.O. Ospedale Careggi - Università
    • FO
      • Cesena, FO, Italy, 47023
        • Ospedale M.Bufalini
      • Forlì, FO, Italy, 47100
        • A.O. Morgagni-Pierantoni
    • GE
      • Genova, GE, Italy, 16132
        • A.O. Ospedale S.Martino
      • Genova, GE, Italy, 16132
        • Istituto Nazionale Ricerca Cancro
      • Genova, GE, Italy, 16133
        • Università-Ospedale san Martino
    • LC
      • Lecco, LC, Italy, 23900
        • Azienda Ospedaliera di Lecco
    • LI
      • Livorno, LI, Italy, 57121
        • Azienda Usl-6 Università
    • LO
      • Casalpusterlengo, LO, Italy, 26841
        • Ospedale di Casalpusterlengo
    • LT
      • Latina, LT, Italy, 04100
        • Azienda USL LT3
    • LU
      • Lido di Camaiore, LU, Italy, 5543
        • Ospedale Unico Versilia
    • Lt
      • Gaeta, Lt, Italy, 04024
        • Centro Oncologico Conti
    • ME
      • Messina, ME, Italy, 98123
        • A.O. Università-Policlinico
    • MI
      • Gorgonzola, MI, Italy, 20064
        • Ospedale Serbelloni
      • Legnano, MI, Italy, 20025
        • Azienda Ospedaliera
      • Magenta, MI, Italy, 20013
        • Azienda Ospedale Civile
      • Milano, MI, Italy, 20100
        • A.O. Ospedale Fatebenefratelli
      • Milano, MI, Italy, 20100
        • A.O. san Paolo
      • Milano, MI, Italy, 20100
        • Casa di Cura Igea
      • Milano, MI, Italy, 20100
        • Istituto dei Tumori
      • Milano, MI, Italy, 20100
        • Istituto di Ricerca S.Raffaele
      • Milano, MI, Italy, 20100
        • Istituto Europeo di Oncologia
      • Milano, MI, Italy, 20100
        • Ospedale Luigi Sacco
      • Milano, MI, Italy, 20123
        • Ospedale S.Carlo Borromeo
      • Monza, MI, Italy, 20052
        • A.O. S.Gerardo
      • Rozzano, MI, Italy, 20133
        • Istituto Clinico Humanitas
      • Sesto San Giovanni, MI, Italy, 20100
        • Multimedica
    • MN
      • Mantova, MN, Italy, 46100
        • A.O. Ospedale carlo Poma
    • MO
      • Carpi, MO, Italy, 41012
        • Ospedale Ramazzini
    • MS
      • Carrara, MS, Italy, 54033
        • USL 1 di Massa e Carrara
    • PA
      • Palermo, PA, Italy, 90100
        • Ospedale Oncologico M.Ascoli
      • Palermo, PA, Italy, 90127
        • Policlinico Giaccone
    • PC
      • Piacenza, PC, Italy, 29100
        • Azienda Ospedale Civile
    • PD
      • Padova, PD, Italy, 35122
        • Istituto Oncologico Veneto
    • PE
      • Penne, PE, Italy, 65100
        • Ospedale Santo Spirito
      • Pescara, PE, Italy, 65100
        • Ospedale Santo Spirito
    • PG
      • Città di Castello, PG, Italy, 06012
        • ASL 1
    • PN
      • Aviano, PN, Italy, 33081
        • Centro Riferimento
      • Pordenone, PN, Italy, 33170
        • A.O. S.Maria degli Angeli
    • PO
      • Prato, PO, Italy, 59100
        • Ospedale ASL 4
    • PR
      • Parma, PR, Italy, 43100
        • Azienda Ospedaliera
    • PS
      • Fano, PS, Italy, 61032
        • Ospedale Santa Croce
      • Pesaro, PS, Italy, 61100
        • A.O. S.Salvatore
    • PZ
      • Potenza, PZ, Italy, 85100
        • Azienda Ospedaliera San Carlo
      • Rionero in Volture, PZ, Italy, 85028
        • Centro Riferimento Oncologico Basilicata
    • RA
      • Faenza, RA, Italy, 48018
        • Ospedale per gli Infermi
      • Lugo, RA, Italy, 48022
        • Ospedale Umberto I
      • Ravenna, RA, Italy, 48100
        • A.O. Santa Maria delle Croci
    • RC
      • Reggio calabria, RC, Italy, 89100
        • Azienda ospedali riuniti
    • RE
      • Reggio Emilia, RE, Italy, 42100
        • A.O. Santa maria Nuova-Spallanzani
    • RM
      • Roma, RM, Italy, 00100
        • Ospedale S.Camillo
      • Roma, RM, Italy, 00100
        • Policlinico Militare Celio
      • Roma, RM, Italy, 00186
        • Università Policlinico Umberto I
      • Roma, RM, Italy, 00189
        • Ospedale Sant'Andrea
    • RN
      • Cattolica, RN, Italy, 47841
        • Azienda Ospedaliera
      • Rimini, RN, Italy, 47900
        • Ospedale Degli Infermi
    • RO
      • Rovigo, RO, Italy, 45100
        • AULSS 18 di Rovigo
    • SO
      • Sondalo, SO, Italy, 23100
        • Ospedale Morelli
      • Sondrio, SO, Italy, 23100
        • A.O. Valtellina e Chiavenna
    • SV
      • Pietra Ligure, SV, Italy, 17027
        • A.O. Santa Corona
    • TO
      • Candiolo, TO, Italy, 10060
        • Università degli Studi
      • Torino, TO, Italy, 10154
        • Ospedale S.Giovanni Bosco
    • UD
      • Latisana, UD, Italy, 33053
        • Ospedale Civile
    • VA
      • Castellanza, VA, Italy, 21053
        • Casa di Cura Santa Maria
    • VI
      • Montecchio Maggiore, VI, Italy, 36075
        • Ulss 5 Ovest Vicentino
    • VR
      • Negrar, VR, Italy, 37126
        • Ospedale Negrar

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:

  • Histologically confirmed AJCC/UICC high-risk stage II or stage III colon cancer . High-risk stage III patients (T4, N+, M0, or any T, N2, M0) may also be further randomized in the BEV study (plus or minus BEV)

  • Stage II patients have to be considered at high-risk if they fulfill >1 of the following criteria:

    • T4 tumours,
    • grade >3,
    • clinical presentation with bowel obstruction or perforation,
    • histological signs of vascular or lymphatic or perineural invasion,
    • <12 nodes examined
  • Age 18 to 75 years
  • Curative surgery no less than 3 ( 4 in the BEV study) and no more than 8 weeks prior to randomization
  • ECOG performance Status (ECOG-PS) <1
  • Signed written informed consent obtained prior to any study specific procedures

Exclusion Criteria:

  • Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections).
  • Previous anti-angiogenic treatment for any malignancy; cytotoxic chemotherapy, radiotherapy or immunotherapy for colon cancer
  • Other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
  • Lactating women
  • Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception
  • History of clinically relevant psychiatric disability , precluding informed consent
  • Clinically relevant cardiovascular disease
  • History or presence of other diseases
  • Evidence of bleeding diathesis or coagulopathy
  • Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes
  • Chronic, daily treatment with high-dose aspirin (>325 mg/day) or clopidogrel (>75 mg/day)
  • Current or recent (within the 28 days prior to randomization) treatment with another investigational drug or participation in another investigational study

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
Experimental: A
FOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 3 months or XELOX (capecitabine and oxaliplatin) for 12 weeks.
Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
To assess whether a 3-month FOLFOX-4 treatment is at least equivalent to a 6-month FOLFOX-4 treatment
Other Names:
  • FOLFOX 3 vs 6
Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
standard treatment
Other Names:
  • FOLFOX 3 vs 6
Active Comparator: B
FOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 6 months or XELOX (capecitabine and oxaliplatin) for 24 weeks.
Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
To assess whether a 3-month FOLFOX-4 treatment is at least equivalent to a 6-month FOLFOX-4 treatment
Other Names:
  • FOLFOX 3 vs 6
Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
standard treatment
Other Names:
  • FOLFOX 3 vs 6

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
disease free survival (DFS)
Time Frame: time from randomization date to date of local or regional relapse
time from randomization date to date of local or regional relapse

Secondary Outcome Measures

Outcome Measure
Time Frame
overall Survival (OS), Toxicity and incidence of adverse events
Time Frame: from the day of randomisation to the date of death from any cause.
from the day of randomisation to the date of death from any cause.

Collaborators and Investigators

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

Sponsor

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Collaborators

Mario Negri Institute for Pharmacological Research

Investigators

  • Principal Investigator: Roberto Labianca, MD, Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
  • Study Chair: Alberto Sobrero, MD, Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

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

June 1, 2007

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

March 17, 2008

First Submitted That Met QC Criteria

March 25, 2008

First Posted (Estimate)

March 28, 2008

Study Record Updates

Last Update Posted (Estimate)

November 26, 2014

Last Update Submitted That Met QC Criteria

November 25, 2014

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2007-000354-31

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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