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

Colon Cancer Clinical Trial

— TOSCA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00646607
• Other study ID #: 2007-000354-31
• Status: Completed
• Phase: Phase 3
• First received: March 17, 2008
• Last updated: November 25, 2014
• Start date: June 2007
• Est. completion date: November 2014

Study information

• Verified date: December 2009
• Source: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical 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 addition to FOLFOX-4 chemotherapy.

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3756
• Est. completion date: November 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colon Cancer

Intervention

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
• FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
standard treatment

Locations

Country	Name	City	State
Italy	Ospedale S.Lazzaro	Alba	CN
Italy	Ospedale di Altamura	Altamura	BA
Italy	A.O. Umberto I -Università Località Torrette	Ancona	AN
Italy	ASL 8 di Arezzo	Arezzo	AR
Italy	Ospedale Mazzoni	Ascoli Piceno	AP
Italy	Ospedale Civile	Asti	AT
Italy	Centro Riferimento	Aviano	PN
Italy	A.O. G.Rummo	Benevento	BN
Italy	Ospedali Riuniti, Largo Barozzi, 1	Bergamo
Italy	Ospedale degli Infermi	Biella	BI
Italy	Ospedale Regionale	Bolzano	BZ
Italy	Fondazione Poliambulanza	Brescia	BS
Italy	Ospedale S.Orsola Fatebenefratelli	Brescia	BS
Italy	Spedali Civili	Brescia	BS
Italy	Università degli Studi	Candiolo	TO
Italy	Ospedale ramazzini	Carpi	MO
Italy	USL 1 di Massa e Carrara	Carrara	MS
Italy	Ospedale Santo Spirito	Casale Monferrato	AL
Italy	Ospedale di Casalpusterlengo	Casalpusterlengo	LO
Italy	A.O. S.Sebastiano	Caserta	CE
Italy	Ospedale S.Leonardo	Castellamare di Stabbia
Italy	Casa di Cura Santa Maria	Castellanza	VA
Italy	Azienda Ospedaliera	Catania	CT
Italy	Azienda ospedaliera	Cattolica	RN
Italy	Ospedale M.Bufalini	Cesena	FO
Italy	ASL 1	Città di Castello	PG
Italy	Ospedale S.Anna	Como	CO
Italy	ospedale Valduce	Como	CO
Italy	Azienda Istituti Ospitalieri	Cremona	CR
Italy	A.O. S.Croce e Carle	Cuneo	CN
Italy	ASL 11	Empoli	FI
Italy	Ospedale Fatebenefratelli Sacra Famiglia	Erba	CO
Italy	Ospedale Profili	Fabriano	AN
Italy	Ospedale per gli Infermi	Faenza	RA
Italy	Ospedale Santa Croce	Fano	PS
Italy	Usl 11 Ospedale Murri	Fermo	AP
Italy	A.O. Careggi-Università, Viale Pieraccini, 17	Firenze
Italy	A.O. Ospedale Careggi - Università	Firenze	FI
Italy	Ospedale S.M.Annunziata-ASL FI	Firenze	FI
Italy	A.O. Morgagni-Pierantoni	Forlì	FO
Italy	Centro Oncologico Conti	Gaeta	Lt
Italy	A.O. Ospedale S.Martino	Genova	GE
Italy	Istituto Nazionale ricerca Cancro	Genova	GE
Italy	Università-Ospedale san Martino	Genova	GE
Italy	Ospedale Serbelloni	Gorgonzola	MI
Italy	Ospedale S.Barbara - Asl 7	Iglesias	CA
Italy	Azienda M.Mellini-Chiara	Iseo	BS
Italy	Università di L'Aquila	L'Aquila	AQ
Italy	ASL 6 - Ospedale Civile	Lamezia Terme	CZ
Italy	AUSL di Lanciano-Vasto	Lanciano	CH
Italy	Azienda USL LT3	Latina	LT
Italy	Ospedale Civile	Latisana	UD
Italy	Azienda Ospedaliera di Lecco	Lecco	LC
Italy	Azienda Ospedaliera	Legnano	MI
Italy	Ospedale Unico Versilia	Lido di Camaiore	LU
Italy	Azienda Usl-6 Università	Livorno	LI
Italy	Ospedale Umberto I	Lugo	RA
Italy	Azienda Ospedale Civile	Magenta	MI
Italy	Ospedale di Manerbio	Manerbio	Bs
Italy	A.O. Ospedale carlo Poma	Mantova	MN
Italy	A.O. Università-Policlinico	Messina	ME
Italy	A.O. Ospedale Fatebenefratelli	Milano	MI
Italy	A.O. san Paolo	Milano	MI
Italy	Casa di Cura Igea	Milano	MI
Italy	Istituto dei Tumori	Milano	MI
Italy	Istituto di Ricerca S.Raffaele	Milano	MI
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Ospedale Luigi Sacco	Milano	MI
Italy	Ospedale S.Carlo Borromeo	Milano	MI
Italy	Policlinico Universitario	Monserrato	CA
Italy	Ulss 5 Ovest Vicentino	Montecchio Maggiore	VI
Italy	P.O. Ospedale S.M. Della Gruccia	Montevarchi	AR
Italy	A.O. s.Gerardo	Monza	MI
Italy	A.O. Cardarelli	Napoli
Italy	Azienda Ospedaliera	Napoli
Italy	Fondazione Pascale - Istituto Tumori	Napoli
Italy	Istituto Tumori- Pascale	Napoli
Italy	Ospedale S.Gennaro	Napoli
Italy	Università federico II	Napoli
Italy	Ospedale Negrar	Negrar	VR
Italy	A.O. Ospedale Maggiore della carità	Novara
Italy	Istituto Oncologico Veneto	Padova	PD
Italy	Ospedale Oncologico M.Ascoli	Palermo	PA
Italy	Policlinico Giaccone	Palermo	PA
Italy	Azienda Ospedaliera	Parma	PR
Italy	Ospedale Santo Spirito	Penne	PE
Italy	A.O. S.Salvatore	Pesaro	PS
Italy	Ospedale Santo Spirito	Pescara	PE
Italy	Azienda Ospedale Civile	Piacenza	PC
Italy	A.O. Santa Corona	Pietra Ligure	SV
Italy	A.O. S.Maria degli Angeli	Pordenone	PN
Italy	Azienda Ospedaliera San Carlo	Potenza	PZ
Italy	Ospedale ASL 4	Prato	PO
Italy	A.O. Santa Maria delle Croci	Ravenna	RA
Italy	Azienda Ospedali Riuniti	Reggio calabria	RC
Italy	A.O. Santa maria Nuova-Spallanzani	Reggio Emilia	RE
Italy	Ospedale degli Infermi	Rimini	RN
Italy	Centro Riferimento Oncologico Basilicata	Rionero in Volture	PZ
Italy	A.O. S.Giovanni Calabita Fatebenefratelli	Roma
Italy	Ospedale S.Camillo	Roma	RM
Italy	Ospedale Sant'Andrea	Roma	RM
Italy	Policlinico Militare Celio	Roma	RM
Italy	Università Campus Biomedico, Via Emilio Longoni, 83	Roma
Italy	Università Policlinico Umberto I	Roma	RM
Italy	AULSS 18 di Rovigo	Rovigo	RO
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	Multimedica	Sesto San Giovanni	MI
Italy	Ospedale Morelli	Sondalo	SO
Italy	A.O. Valtellina e Chiavenna	Sondrio	SO
Italy	Ospedale S.Giovanni Bosco	Torino	TO
Italy	A.O. Treviglio-Caravaggio, P.le Ospedale n1	Treviglio	Bergamo

Sponsors (2)

Lead Sponsor	Collaborator
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente	Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease free survival (DFS)		time from randomization date to date of local or regional relapse	No
Secondary	overall Survival (OS), Toxicity and incidence of adverse events		from the day of randomisation to the date of death from any cause.	Yes