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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2009 by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Sponsor:
Collaborator:
Mario Negri Institute for Pharmacological Research
Information provided by (Responsible Party):
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
ClinicalTrials.gov Identifier:
NCT00646607
First received: March 17, 2008
Last updated: September 3, 2013
Last verified: December 2009
  Purpose

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 ]

Estimated Enrollment: 4100
Study Start Date: June 2007
Estimated Study Completion Date: December 2015
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
3-month FOLFOX-4 (Oxaliplatin, leucovorin and 5-fluorouracil )
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
6 months FOLFOX-4(Oxaliplatin, leucovorin and 5-fluorouracil )
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.

  Eligibility

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00646607

Contacts
Contact: Roberto Labianca, MD +39 035 269859 rlabian@tin.it
Contact: Silvia Rota, Data Manager +39 0331 490052 centrotrialgiscad@yahoo.it

  Hide Study Locations
Locations
Italy
Ospedale Santo Spirito Not yet recruiting
Casale Monferrato, AL, Italy, 15033
Principal Investigator: Mario Botta, MD         
A.O. Umberto I -Università Località Torrette Recruiting
Ancona, AN, Italy, 62020
Sub-Investigator: Stefano Cascinu, MD         
Ospedale Profili Recruiting
Fabriano, AN, Italy, 60044
Sub-Investigator: Rosa R Silva, MD         
Ospedale Mazzoni Recruiting
Ascoli Piceno, AP, Italy, 63100
Sub-Investigator: Lucia Angelelli, MD         
Usl 11 Ospedale Murri Recruiting
Fermo, AP, Italy, 63023
Sub-Investigator: Lucio Giustini, MD         
Università di L'Aquila Recruiting
L'Aquila, AQ, Italy, 67100
Principal Investigator: Corrado Ficorella, MD         
ASL 8 di Arezzo Recruiting
Arezzo, AR, Italy, 52100
Principal Investigator: Michele Sisani, MD         
P.O. Ospedale S.M. Della Gruccia Recruiting
Montevarchi, AR, Italy, 52025
Principal Investigator: Michela Rinaldini, MD         
Ospedale Civile Recruiting
Asti, AT, Italy, 14100
Sub-Investigator: Franco Testore, MD         
Ospedale di Altamura Recruiting
Altamura, BA, Italy, 70100
Principal Investigator: Giacomo Vessia, MD         
A.O. Treviglio-Caravaggio, P.le Ospedale n1 Recruiting
Treviglio, Bergamo, Italy, 24047
Sub-Investigator: sandro Barni, MD         
Ospedale degli Infermi Not yet recruiting
Biella, BI, Italy, 13900
Sub-Investigator: Mario Clerico, MD         
A.O. G.Rummo Recruiting
Benevento, BN, Italy, 82100
Principal Investigator: Bruno Daniele, MD         
Ospedale S.Orsola Fatebenefratelli Recruiting
Brescia, BS, Italy, 15100
Sub-Investigator: Giordano D Beretta, MD         
Fondazione Poliambulanza Recruiting
Brescia, BS, Italy, 15100
Sub-Investigator: Alberto Zaniboni, MD         
Spedali Civili Recruiting
Brescia, BS, Italy, 25100
Sub-Investigator: Giovanni Marini, MD         
Principal Investigator: Giovanni Rangoni, MD         
Azienda M.Mellini-Chiara Recruiting
Iseo, BS, Italy, 25049
Principal Investigator: Giuseppina Arcangeli, MD         
Ospedale di Manerbio Recruiting
Manerbio, Bs, Italy, 25025
Sub-Investigator: Giuseppe Colosini, MD         
Ospedale Regionale Recruiting
Bolzano, BZ, Italy, 39100
Principal Investigator: Claudio Graiff, MD         
Ospedale S.Barbara - Asl 7 Not yet recruiting
Iglesias, CA, Italy, 09016
Principal Investigator: Luciano Virdis, MD         
Policlinico Universitario Recruiting
Monserrato, CA, Italy, 09042
Principal Investigator: Bruno Massidda, MD         
Sub-Investigator: Giovanni Mantovani, MD         
A.O. S.Sebastiano Not yet recruiting
Caserta, CE, Italy, 81100
Principal Investigator: Giovanni P Ianniello, MD         
AUSL di Lanciano-Vasto Not yet recruiting
Lanciano, CH, Italy, 66034
Principal Investigator: Domenico Nuzzo, MD         
Ospedale S.Lazzaro Recruiting
Alba, CN, Italy, 12051
Principal Investigator: Roberto Faggiuolo, MD         
A.O. S.Croce e Carle Recruiting
Cuneo, CN, Italy, 12100
Sub-Investigator: Marco C Merlano, MD         
Ospedale S.Anna Recruiting
Como, CO, Italy, 22100
Principal Investigator: Monica Giordano, MD         
ospedale Valduce Recruiting
Como, CO, Italy, 22100
Sub-Investigator: Maria Duro, MD         
Ospedale Fatebenefratelli Sacra Famiglia Not yet recruiting
Erba, CO, Italy, 22036
Principal Investigator: Alfonso Sala, MD         
Azienda Istituti Ospitalieri Recruiting
Cremona, CR, Italy, 26100
Principal Investigator: Rodolfo Passalacqua, MD         
Azienda Ospedaliera Recruiting
Catania, CT, Italy, 95100
Principal Investigator: Calogero Buscarino, MD         
ASL 6 - Ospedale Civile Recruiting
Lamezia Terme, CZ, Italy, 88046
Principal Investigator: Ettore Greco, MD         
ASL 11 Not yet recruiting
Empoli, FI, Italy, 50010
Principal Investigator: Gianmaria Fiorentini, MD         
A.O. Ospedale Careggi - Università Not yet recruiting
Firenze, FI, Italy, 50100
Sub-Investigator: Enrico Mini, MD         
Principal Investigator: Roberto Mazzanti, MD         
Ospedale S.M.Annunziata-ASL FI Not yet recruiting
Firenze, FI, Italy, 50011
Principal Investigator: Angela S Ribecco, MD         
Ospedale M.Bufalini Recruiting
Cesena, FO, Italy, 47023
Sub-Investigator: Marina Faedi, MD         
A.O. Morgagni-Pierantoni Recruiting
Forlì, FO, Italy, 47100
Sub-Investigator: Dino Amadori, MD         
A.O. Ospedale S.Martino Recruiting
Genova, GE, Italy, 16132
Sub-Investigator: Alberto Sobrero, MD         
Università-Ospedale san Martino Recruiting
Genova, GE, Italy, 16133
Sub-Investigator: Lucia Tixi, MD         
Istituto Nazionale ricerca Cancro Recruiting
Genova, GE, Italy, 16132
Principal Investigator: Silvana Chiara, MD         
Azienda Ospedaliera di Lecco Recruiting
Lecco, LC, Italy, 23900
Sub-Investigator: Giovanni Ucci, MD         
Azienda Usl-6 Università Recruiting
Livorno, LI, Italy, 57121
Sub-Investigator: Alfredo Falcone, MD         
Ospedale di Casalpusterlengo Recruiting
Casalpusterlengo, LO, Italy, 26841
Principal Investigator: Roberto Franchi, MD         
Centro Oncologico Conti Recruiting
Gaeta, Lt, Italy, 04024
Principal Investigator: Enzo Veltri, MD         
Azienda USL LT3 Not yet recruiting
Latina, LT, Italy, 04100
Principal Investigator: Modesto D'Aprile, MD         
Ospedale Unico Versilia Recruiting
Lido di Camaiore, LU, Italy, 5543
Principal Investigator: Domenico Amoroso, MD         
A.O. Università-Policlinico Recruiting
Messina, ME, Italy, 98123
Principal Investigator: Vincenzo Adamo, MD         
Ospedale Serbelloni Recruiting
Gorgonzola, MI, Italy, 20064
Sub-Investigator: Luciano Isa, MD         
Azienda Ospedaliera Recruiting
Legnano, MI, Italy, 20025
Principal Investigator: Antonio Luoni, MD         
Azienda Ospedale Civile Not yet recruiting
Magenta, MI, Italy, 20013
Principal Investigator: Alberto DePaoli, MD         
Istituto di Ricerca S.Raffaele Recruiting
Milano, MI, Italy, 20100
Sub-Investigator: Eugenio Villa, MD         
Casa di Cura Igea Recruiting
Milano, MI, Italy, 20100
Sub-Investigator: Gianfranco Pancera, MD         
Istituto dei Tumori Recruiting
Milano, MI, Italy, 20100
Sub-Investigator: Emilio Bajetta, MD         
A.O. san Paolo Recruiting
Milano, MI, Italy, 20100
Sub-Investigator: Paolo Foa, MD         
A.O. Ospedale Fatebenefratelli Recruiting
Milano, MI, Italy, 20100
Principal Investigator: Gabriella Farina, MD         
Istituto Europeo di Oncologia Recruiting
Milano, MI, Italy, 20100
Principal Investigator: Filippo DeBraud, MD         
Ospedale Luigi Sacco Recruiting
Milano, MI, Italy, 20100
Principal Investigator: Elena Piazza, MD         
Ospedale S.Carlo Borromeo Recruiting
Milano, MI, Italy, 20123
Sub-Investigator: Donata Tabiadon, MD         
A.O. s.Gerardo Recruiting
Monza, MI, Italy, 20052
Sub-Investigator: Paolo Bidoli, MD         
Istituto Clinico Humanitas Recruiting
Rozzano, MI, Italy, 20133
Principal Investigator: Armando Santoro, MD         
Multimedica Recruiting
Sesto San Giovanni, MI, Italy, 20100
Principal Investigator: Ornella Gottardi, MD         
A.O. Ospedale carlo Poma Recruiting
Mantova, MN, Italy, 46100
Principal Investigator: Enrico Aitini, MD         
Ospedale ramazzini Recruiting
Carpi, MO, Italy, 41012
Sub-Investigator: Fabrizio Artioli, MD         
USL 1 di Massa e Carrara Recruiting
Carrara, MS, Italy, 54033
Principal Investigator: Maurizio Cantore, MD         
Ospedale Oncologico M.Ascoli Not yet recruiting
Palermo, PA, Italy, 90100
Principal Investigator: Biagio Agostara, MD         
Policlinico Giaccone Recruiting
Palermo, PA, Italy, 90127
Principal Investigator: Sergio Palmeri, MD         
Azienda Ospedale Civile Recruiting
Piacenza, PC, Italy, 29100
Principal Investigator: Giuseppe Cavanna, MD         
Istituto Oncologico Veneto Recruiting
Padova, PD, Italy, 35122
Principal Investigator: Sara Lonardi, MD         
Sub-Investigator: Donato Nitti, MD         
Ospedale Santo Spirito Recruiting
Penne, PE, Italy, 65100
Principal Investigator: Donato Natale, MD         
Ospedale Santo Spirito Recruiting
Pescara, PE, Italy, 65100
Principal Investigator: Marco Lombardo, MD         
ASL 1 Recruiting
Città di Castello, PG, Italy, 06012
Principal Investigator: Stefano Bravi, MD         
Centro Riferimento Recruiting
Aviano, PN, Italy, 33081
Sub-Investigator: Sergio Frustaci, MD         
A.O. S.Maria degli Angeli Recruiting
Pordenone, PN, Italy, 33170
Sub-Investigator: Salvatore Tumolo, MD         
Ospedale ASL 4 Recruiting
Prato, PO, Italy, 59100
Principal Investigator: Angelo Di Leo, MD         
Azienda Ospedaliera Recruiting
Parma, PR, Italy, 43100
Principal Investigator: Francesco leonardi, MD         
Ospedale Santa Croce Recruiting
Fano, PS, Italy, 61032
Principal Investigator: Rodolfo Mattioli, MD         
A.O. S.Salvatore Recruiting
Pesaro, PS, Italy, 61100
Principal Investigator: Vincenzo Catalano, MD         
Azienda Ospedaliera San Carlo Recruiting
Potenza, PZ, Italy, 85100
Principal Investigator: Giuseppe Rosati, MD         
Centro Riferimento Oncologico Basilicata Recruiting
Rionero in Volture, PZ, Italy, 85028
Sub-Investigator: Anna M Bochicchio, MD         
Ospedale per gli Infermi Recruiting
Faenza, RA, Italy, 48018
Sub-Investigator: Angelo Gambi, MD         
Ospedale Umberto I Recruiting
Lugo, RA, Italy, 48022
Sub-Investigator: Giorgio Cruciani, MD         
A.O. Santa Maria delle Croci Recruiting
Ravenna, RA, Italy, 48100
Sub-Investigator: Maurizio Marangolo, MD         
Azienda Ospedali Riuniti Recruiting
Reggio calabria, RC, Italy, 89100
Sub-Investigator: Mario Nardi, MD         
A.O. Santa maria Nuova-Spallanzani Recruiting
Reggio Emilia, RE, Italy, 42100
Sub-Investigator: Corrado Boni, MD         
Ospedale S.Camillo Recruiting
Roma, RM, Italy, 00100
Principal Investigator: Andrea Mancuso, MD         
Policlinico Militare Celio Active, not recruiting
Roma, RM, Italy, 00100
Ospedale Sant'Andrea Recruiting
Roma, RM, Italy, 00189
Principal Investigator: Andrea Marchetti, MD         
Università Policlinico Umberto I Recruiting
Roma, RM, Italy, 00186
Sub-Investigator: Enrico Cortesi, MD         
Sub-Investigator: Marina DeSeri, MD         
Azienda ospedaliera Recruiting
Cattolica, RN, Italy, 47841
Sub-Investigator: Enzo Pasquini, MD         
Ospedale degli Infermi Recruiting
Rimini, RN, Italy, 47900
Sub-Investigator: Alberto Ravaioli, MD         
AULSS 18 di Rovigo Recruiting
Rovigo, RO, Italy, 45100
Principal Investigator: Felice Pasini, MD         
Ospedale Morelli Recruiting
Sondalo, SO, Italy, 23100
Principal Investigator: Giuseppe Valmadre, MD         
A.O. Valtellina e Chiavenna Recruiting
Sondrio, SO, Italy, 23100
Sub-Investigator: Alessandro Bertolini, MD         
A.O. Santa Corona Recruiting
Pietra Ligure, SV, Italy, 17027
Sub-Investigator: Ugo Folco, MD         
Università degli Studi Recruiting
Candiolo, TO, Italy, 10060
Sub-Investigator: Massimo Aglietta, MD         
Ospedale S.Giovanni Bosco Recruiting
Torino, TO, Italy, 10154
Sub-Investigator: Guido Vietti Ramus, MD         
Ospedale Civile Recruiting
Latisana, UD, Italy, 33053
Principal Investigator: Aldo Iop, MD         
Casa di Cura Santa Maria Recruiting
Castellanza, VA, Italy, 21053
Principal Investigator: Eraldo Bucci, MD         
Ulss 5 Ovest Vicentino Not yet recruiting
Montecchio Maggiore, VI, Italy, 36075
Principal Investigator: Cristina Oliani, MD         
Ospedale Negrar Recruiting
Negrar, VR, Italy, 37126
Principal Investigator: Marco Venturini, MD         
Ospedali Riuniti, Largo Barozzi, 1 Recruiting
Bergamo, Italy, 24128
Principal Investigator: Roberto Labianca, MD         
Ospedale S.Leonardo Not yet recruiting
Castellamare di Stabbia, Italy, 80053
Principal Investigator: Maddalena Bianco, MD         
A.O. Careggi-Università, Viale Pieraccini, 17 Recruiting
Firenze, Italy, 50139
Sub-Investigator: Francesco Di Costanzo, MD         
Azienda Ospedaliera Recruiting
Napoli, Italy, 80131
Principal Investigator: Vincenzo Montesarchio, MD         
Ospedale S.Gennaro Not yet recruiting
Napoli, Italy, 80131
Principal Investigator: Luigi Maiorino, MD         
A.O. Cardarelli Recruiting
Napoli, Italy, 80131
Principal Investigator: Giacomo Cartenì, MD         
Università federico II Recruiting
Napoli, Italy, 80130
Principal Investigator: Sabino DePlacido, MD         
Fondazione Pascale - Istituto Tumori Recruiting
Napoli, Italy, 80130
Principal Investigator: Giuseppe Iaffaioli, MD         
Istituto Tumori- Pascale Recruiting
Napoli, Italy, 80130
Principal Investigator: Giuseppe Comella, MD         
A.O. Ospedale Maggiore della carità Recruiting
Novara, Italy, 28100
Principal Investigator: Oscar Alabiso, MD         
Università Campus Biomedico, Via Emilio Longoni, 83 Recruiting
Roma, Italy, 00155
Principal Investigator: Giuseppe Tonini, MPr         
A.O. S.Giovanni Calabita Fatebenefratelli Recruiting
Roma, Italy, 00186
Principal Investigator: Domenico Corsi, MD         
Sponsors and Collaborators
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
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
  More Information

No publications provided

Responsible Party: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
ClinicalTrials.gov Identifier: NCT00646607     History of Changes
Other Study ID Numbers: 2007-000354-31
Study First Received: March 17, 2008
Last Updated: September 3, 2013
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:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Bevacizumab
Oxaliplatin
Fluorouracil
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on September 30, 2014