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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)
* Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>FOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 3 months or XELOX (capecitabine and oxaliplatin) for 12 weeks. | Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)<br>* To assess whether a 3-month FOLFOX-4 treatment is at least equivalent to a 6-month FOLFOX-4 treatment<br>* Other names: FOLFOX 3 vs 6;|
| Active Comparator: B<br>FOLFOX-4 (infusional 5-Fluouracil, leucovorin and oxaliplatin) for 6 months or XELOX (capecitabine and oxaliplatin) for 24 weeks. | Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin)<br>* standard treatment<br>* Other names: FOLFOX 3 vs 6;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival (DFS) |  | time from randomization date to date of local or regional relapse | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall Survival (OS), Toxicity and incidence of adverse events |  | from the day of randomisation to the date of death from any cause. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal neoplasm, high risk, stage II/III