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

This study has been completed.
Mario Negri Institute for Pharmacological Research
Information provided by (Responsible Party):
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente Identifier:
First received: March 17, 2008
Last updated: November 25, 2014
Last verified: December 2009

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.

Condition Intervention Phase
Colon Cancer
Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente:

Primary Outcome Measures:
  • disease free survival (DFS) [ Time Frame: time from randomization date to date of local or regional relapse ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall Survival (OS), Toxicity and incidence of adverse events [ Time Frame: from the day of randomisation to the date of death from any cause. ] [ Designated as safety issue: Yes ]

Enrollment: 3756
Study Start Date: June 2007
Study Completion Date: November 2014
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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)
standard treatment
Other Name: FOLFOX 3 vs 6

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.

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00646607

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

No publications provided

Responsible Party: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente Identifier: NCT00646607     History of Changes
Other Study ID Numbers: 2007-000354-31
Study First Received: March 17, 2008
Last Updated: November 25, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente:
colorectal neoplasm
high risk
stage II/III

Additional relevant MeSH terms:
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses processed this record on November 25, 2015