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

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Status and phase

Completed

Phase 3

Conditions

Colon Cancer

Treatments

Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)

Study type

Interventional

Funder types

Other

Identifiers

NCT00646607

2007-000354-31

Details and patient eligibility

About

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.

Full 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.

Enrollment

3,756 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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