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Colon CancerPhase 3TOSCANCT00646607

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

A Phase 3 study testing FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin) in people with Colon Cancer, run by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente at 111 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Colon Cancer
What is being tested?
FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,756 participants
Where
111 sitesItaly
Study dates
Jun 2007to Nov 2014
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
Show all 11Show fewer
  • <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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

111 sites in 1 country.

111 sites in 1 country

Italy111 sites

  • Ospedale S.Lazzaro

    Alba, CN, 12051

  • Ospedale di Altamura

    Altamura, BA, 70100

  • A.O. Umberto I -Università Località Torrette

    Ancona, AN, 62020

  • ASL 8 di Arezzo

    Arezzo, AR, 52100

  • Ospedale Mazzoni

    Ascoli Piceno, AP, 63100

  • Ospedale Civile

    Asti, AT, 14100

  • Centro Riferimento

    Aviano, PN, 33081

  • A.O. G.Rummo

    Benevento, BN, 82100

  • Ospedali Riuniti, Largo Barozzi, 1

    Bergamo, Bergamo, 24128

  • Ospedale degli Infermi

    Biella, BI, 13900

  • Ospedale Regionale

    Bolzano, BZ, 39100

  • Fondazione Poliambulanza

    Brescia, BS, 15100

  • Ospedale S.Orsola Fatebenefratelli

    Brescia, BS, 15100

  • Spedali Civili

    Brescia, BS, 25100

  • Università degli Studi

    Candiolo, TO, 10060

  • Ospedale ramazzini

    Carpi, MO, 41012

  • USL 1 di Massa e Carrara

    Carrara, MS, 54033

  • Ospedale Santo Spirito

    Casale Monferrato, AL, 15033

  • Ospedale di Casalpusterlengo

    Casalpusterlengo, LO, 26841

  • A.O. S.Sebastiano

    Caserta, CE, 81100

  • Ospedale S.Leonardo

    Castellamare Di Stabbia, 80053

  • Casa di Cura Santa Maria

    Castellanza, VA, 21053

  • Azienda Ospedaliera

    Catania, CT, 95100

  • Azienda ospedaliera

    Cattolica, RN, 47841

  • Ospedale M.Bufalini

    Cesena, FO, 47023

  • ASL 1

    Città di Castello, PG, 06012

  • Ospedale S.Anna

    Como, CO, 22100

  • ospedale Valduce

    Como, CO, 22100

  • Azienda Istituti Ospitalieri

    Cremona, CR, 26100

  • A.O. S.Croce e Carle

    Cuneo, CN, 12100

  • ASL 11

    Empoli, FI, 50010

  • Ospedale Fatebenefratelli Sacra Famiglia

    Erba, CO, 22036

  • Ospedale Profili

    Fabriano, AN, 60044

  • Ospedale per gli Infermi

    Faenza, RA, 48018

  • Ospedale Santa Croce

    Fano, PS, 61032

  • Usl 11 Ospedale Murri

    Fermo, AP, 63023

  • A.O. Careggi-Università, Viale Pieraccini, 17

    Florence, Firenze, 50139

  • Ospedale S.M.Annunziata-ASL FI

    Florence, FI, 50011

  • A.O. Ospedale Careggi - Università

    Florence, FI, 50100

  • A.O. Morgagni-Pierantoni

    Forlì, FO, 47100

  • Centro Oncologico Conti

    Gaeta, Lt, 04024

  • A.O. Ospedale S.Martino

    Genova, GE, 16132

  • Istituto Nazionale ricerca Cancro

    Genova, GE, 16132

  • Università-Ospedale san Martino

    Genova, GE, 16133

  • Ospedale Serbelloni

    Gorgonzola, MI, 20064

  • Ospedale S.Barbara - Asl 7

    Iglesias, CA, 09016

  • Azienda M.Mellini-Chiara

    Iseo, BS, 25049

  • Università di L'Aquila

    L’Aquila, AQ, 67100

  • ASL 6 - Ospedale Civile

    Lamezia Terme, CZ, 88046

  • AUSL di Lanciano-Vasto

    Lanciano, CH, 66034

  • Azienda USL LT3

    Latina, LT, 04100

  • Ospedale Civile

    Latisana, UD, 33053

  • Azienda Ospedaliera di Lecco

    Lecco, LC, 23900

  • Azienda Ospedaliera

    Legnano, MI, 20025

  • Ospedale Unico Versilia

    Lido di Camaiore, LU, 5543

  • Azienda Usl-6 Università

    Livorno, LI, 57121

  • Ospedale Umberto I

    Lugo, RA, 48022

  • Azienda Ospedale Civile

    Magenta, MI, 20013

  • Ospedale di Manerbio

    Manerbio, Bs, 25025

  • A.O. Ospedale carlo Poma

    Mantua, MN, 46100

  • A.O. Università-Policlinico

    Messina, ME, 98123

  • A.O. Ospedale Fatebenefratelli

    Milan, MI, 20100

  • A.O. san Paolo

    Milan, MI, 20100

  • Casa di Cura Igea

    Milan, MI, 20100

  • Istituto dei Tumori

    Milan, MI, 20100

  • Istituto di Ricerca S.Raffaele

    Milan, MI, 20100

  • Istituto Europeo di Oncologia

    Milan, MI, 20100

  • Ospedale Luigi Sacco

    Milan, MI, 20100

  • Ospedale S.Carlo Borromeo

    Milan, MI, 20123

  • Policlinico Universitario

    Monserrato, CA, 09042

  • Ulss 5 Ovest Vicentino

    Montecchio Maggiore, VI, 36075

  • P.O. Ospedale S.M. Della Gruccia

    Montevarchi, AR, 52025

  • A.O. s.Gerardo

    Monza, MI, 20052

  • Fondazione Pascale - Istituto Tumori

    Naples, 80130

  • Istituto Tumori- Pascale

    Naples, 80130

  • Università federico II

    Naples, 80130

  • A.O. Cardarelli

    Naples, 80131

  • Azienda Ospedaliera

    Naples, 80131

  • Ospedale S.Gennaro

    Naples, 80131

  • Ospedale Negrar

    Negrar, VR, 37126

  • A.O. Ospedale Maggiore della carità

    Novara, 28100

  • Istituto Oncologico Veneto

    Padova, PD, 35122

  • Ospedale Oncologico M.Ascoli

    Palermo, PA, 90100

  • Policlinico Giaccone

    Palermo, PA, 90127

  • Azienda Ospedaliera

    Parma, PR, 43100

  • Ospedale Santo Spirito

    Penne, PE, 65100

  • A.O. S.Salvatore

    Pesaro, PS, 61100

  • Ospedale Santo Spirito

    Pescara, PE, 65100

  • Azienda Ospedale Civile

    Piacenza, PC, 29100

  • A.O. Santa Corona

    Pietra Ligure, SV, 17027

  • A.O. S.Maria degli Angeli

    Pordenone, PN, 33170

  • Azienda Ospedaliera San Carlo

    Potenza, PZ, 85100

  • Ospedale ASL 4

    Prato, PO, 59100

  • A.O. Santa Maria delle Croci

    Ravenna, RA, 48100

  • Azienda Ospedali Riuniti

    Reggio Calabria, RC, 89100

  • A.O. Santa maria Nuova-Spallanzani

    Reggio Emilia, RE, 42100

  • Ospedale degli Infermi

    Rimini, RN, 47900

  • Centro Riferimento Oncologico Basilicata

    Rionero in Volture, PZ, 85028

  • Ospedale S.Camillo

    Roma, RM, 00100

  • Policlinico Militare Celio

    Roma, RM, 00100

  • Università Policlinico Umberto I

    Roma, RM, 00186

  • Ospedale Sant'Andrea

    Roma, RM, 00189

  • Università Campus Biomedico, Via Emilio Longoni, 83

    Roma, Roma, 00155

  • A.O. S.Giovanni Calabita Fatebenefratelli

    Roma, Roma, 00186

  • AULSS 18 di Rovigo

    Rovigo, RO, 45100

  • Istituto Clinico Humanitas

    Rozzano, MI, 20133

  • Multimedica

    Sesto San Giovanni, MI, 20100

  • Ospedale Morelli

    Sondalo, SO, 23100

  • A.O. Valtellina e Chiavenna

    Sondrio, SO, 23100

  • Ospedale S.Giovanni Bosco

    Torino, TO, 10154

  • A.O. Treviglio-Caravaggio, P.le Ospedale n1

    Treviglio, Bergamo, 24047

Other trials in Italy

About this study

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

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.

Read the 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.

Conditions
Colon Cancer
Being tested
FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
Keywords
colorectal neoplasm, high risk, stage II/III
Medical subject headings
Colonic Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)Drug

    Also called FOLFOX 3 vs 6

    To assess whether a 3-month FOLFOX-4 treatment is at least equivalent to a 6-month FOLFOX-4 treatment

  • FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)Drug

    Also called FOLFOX 3 vs 6

    standard treatment

Study groups in NCT00646607
Study groupRoleWhat they receive
AExperimentalFOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 3 months or XELOX (capecitabine and oxaliplatin) for 12 weeks.
Receives: Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
BActive comparatorFOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 6 months or XELOX (capecitabine and oxaliplatin) for 24 weeks.
Receives: Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. disease free survival (DFS)

    Measured: time from randomization date to date of local or regional relapse

Secondary outcomes (1)

  1. overall Survival (OS), Toxicity and incidence of adverse events

    Measured: from the day of randomisation to the date of death from any cause.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2008 (estimated)
  2. Study startJun 2007
  3. Primary completionApr 2013
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3,756 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00646607
Sponsor's protocol ID
2007-000354-31
Acronym
TOSCA
Status last verified
Dec 2009
First submitted
17 Mar 2008
Last updated
26 Nov 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.

    PubMed 36306483

  • Iveson TJ, Sobrero AF, Yoshino T, Souglakos I, Ou FS, Meyers JP, Shi Q, Grothey A, Saunders MP, Labianca R, Yamanaka T, Boukovinas I, Hollander NH, Galli F, Yamazaki K, Georgoulias V, Kerr R, Oki E, Lonardi S, Harkin A, Rosati G, Paul J. Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer. J Clin Oncol. 2021 Feb 20;39(6):631-641. doi: 10.1200/JCO.20.01330. Epub 2021 Jan 13.

    PubMed 33439695

  • Sobrero A, Lonardi S, Rosati G, Di Bartolomeo M, Ronzoni M, Pella N, Scartozzi M, Banzi M, Zampino MG, Pasini F, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Barni S, Rulli E, Labianca R; TOSCA Investigators. FOLFOX or CAPOX in Stage II to III Colon Cancer: Efficacy Results of the Italian Three or Six Colon Adjuvant Trial. J Clin Oncol. 2018 May 20;36(15):1478-1485. doi: 10.1200/JCO.2017.76.2187. Epub 2018 Apr 5.

    PubMed 29620994

  • Lonardi S, Sobrero A, Rosati G, Di Bartolomeo M, Ronzoni M, Aprile G, Massida B, Scartozzi M, Banzi M, Zampino MG, Pasini F, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Barni S, Zagonel V, Maiello E, Rulli E, Labianca R; TOSCA (Three or Six Colon Adjuvant) Investigators. Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial. Ann Oncol. 2016 Nov;27(11):2074-2081. doi: 10.1093/annonc/mdw404. Epub 2016 Aug 29.

    PubMed 27573560

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin) in people with Colon Cancer, run by Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente at 111 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 111 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

disease free survival (DFS) (time frame: time from randomization date to date of local or regional relapse). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00646607, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2014; AzTrials last refreshed its copy on 8 Nov 2026.

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