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

Sponsor:	Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Collaborator:	Mario Negri Institute for Pharmacological Research
Information provided by:	Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
ClinicalTrials.gov Identifier:	NCT00646607

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Bevacizumab Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

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 Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental 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
B: Active Comparator 6 months FOLFOX-4(Oxaliplatin, leucovorin and 5-fluorouracil )	Drug: FOLFOX (Oxaliplatin, 5Fluorouracil, Lederfolin) standard treatment

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

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

Show 111 Study Locations

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:	GISCAD ( Roberto Labianca GISCAD President )
Study ID Numbers:	2007-000354-31
Study First Received:	March 17, 2008
Last Updated:	December 14, 2009
ClinicalTrials.gov Identifier:	NCT00646607 History of Changes
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:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Colonic Diseases
Physiological Effects of Drugs
Leucovorin
Bevacizumab
Oxaliplatin
Neoplasms by Site
Vitamins
Therapeutic Uses
Growth Inhibitors

Angiogenesis Modulating Agents
Micronutrients
Digestive System Neoplasms
Vitamin B Complex
Growth Substances
Intestinal Diseases
Angiogenesis Inhibitors
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Colonic Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010