Combination Chemotherapy With or Without Cetuximab in Treating Patients With Stage III Colon Cancer That Was Completely Removed By Surgery

Colorectal Cancer Clinical Trial

Official title:

Adjuvant Treatment of Fully Resected Stage III Colon Cancer With FOLFOX-4 Versus FOLFOX-4 Plus Cetuximab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00265811
• Other study ID #: CDR0000453839
• Secondary ID: FFCD-PETACC-8EU-
• Status: Completed
• Phase: Phase 3
• Start date: November 2005
• Est. completion date: June 22, 2010

Study information

• Verified date: November 2020
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, or fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy with or without cetuximab after surgery may kill any remaining tumor cells and keep colon cancer from coming back. It is not yet known whether giving combination chemotherapy together with cetuximab is more effective than giving combination chemotherapy alone in treating colon cancer.

PURPOSE: This randomized phase III trial is studying combination chemotherapy and cetuximab to see how well they work compared to combination chemotherapy alone in treating patients with stage III colon cancer that was completely removed by surgery.

Description:

OBJECTIVES:

Primary

• Compare the disease-free survival rates in patients with completely resected stage III colon cancer treated with adjuvant oxaliplatin, leucovorin calcium, and fluorouracil with vs without cetuximab.

Secondary

• Compare the 3-year disease-free survival rate and 5-year overall survival rate in patients treated with these regimens.

• Compare the overall survival of patients treated with these regimens.

• Compare the treatment compliance of patients treated with these regimens.

• Determine the prognostic factors and markers predictive for relapse and/or treatment efficacy in patients treated with these regimens.

• Compare the safety of these regimens in these patients.

OUTLINE: This is an open-label, randomized, controlled, multicenter study. Patients are stratified according to obstruction/perforation status (no obstruction and no perforation vs obstruction and/or perforation), N stage (N1 vs N2), and T stage (T1-3 vs T4). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 22 hours on days 1 and 2.

• Arm II: Patients receive chemotherapy as in arm I plus cetuximab IV over 1-2 hours on days 1 and 8.

In both arms, treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for approximately 5 years.

PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2559
• Est. completion date: June 22, 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III adenocarcinoma of the colon

• Must have undergone curative resection (R0) within the past 28-56 days

• No radiotherapy prior to surgery

• carcinoembryonic antigen (CEA) = 1.5 times upper limit of normal (ULN) after surgery

• No rectal cancer located within 15 cm from the anal verge by endoscopy or under the peritoneal reflection at surgery

• No metastatic spread at baseline assessment

• No prior or concurrent CNS disease by physical exam

PATIENT CHARACTERISTICS:

Performance status

• WHO 0-1

Life expectancy

• At least 5 years

Hematopoietic

• WBC = 3,000/mm^3

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9 g/dL

Hepatic

• Bilirubin = 1.5 times ULN

• AST and ALT = 2.5 times ULN

• Alkaline phosphatase = 1.5 times ULN

Renal

• Creatinine = 1.5 times ULN

Cardiovascular

• No coronary artery disease

• No myocardial infarction within the past 12 months

• No high risk of uncontrolled arrhythmia

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No inflammatory bowel disease

• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix

• No significant traumatic injury within the past 28 days

• No known hypersensitivity to any of the components of the study drugs

• No medical, geographical, sociological, psychological, or legal condition that would preclude study participation

• No peripheral neuropathy = grade 1

• No other significant disease that would preclude study participation

PRIOR CONCURRENT THERAPY:

Chemotherapy

• No prior chemotherapy

Radiotherapy

• See Disease Characteristics

• No prior abdominal or pelvic irradiation

Surgery

• See Disease Characteristics

• Recovered from prior surgery

• More than 28 days since prior major surgical procedure or open biopsy

• No concurrent major surgical procedure

Related Conditions & MeSH terms

• Colonic Neoplasms
• Colorectal Cancer

Intervention

Drug:
• Folfox

• Cetuximab

Locations

Country	Name	City	State
France	Hopital Duffaut	Avignon
France	CHU de Caen	Caen
France	Hopital Robert Boulin	Libourne
France	CHU Pitie-Salpetriere	Paris
France	Hopital Bichat - Claude Bernard	Paris
France	Hopital Tenon	Paris
France	Centre Hospitalier Yves Le Foll	Saint Brieuc Cedex 1
France	Nouvelle Clinique Generale	Valence

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

References & Publications (2)

Taieb J, Puig PL, Bedenne L. Cetuximab plus FOLFOX-4 for fully resected stage III colon carcinoma: scientific background and the ongoing PETACC-8 trial. Expert Rev Anticancer Ther. 2008 Feb;8(2):183-9. doi: 10.1586/14737140.8.2.183. — View Citation

Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, Thaler J, Bridgewater J, Petersen LN, Blons H, Collette L, Van Cutsem E, Rougier P, Salazar R, Bedenne L, Emile JF, Laurent-Puig P, Lepage C; PETACC-8 Study Investigators. Oxaliplatin, f — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival	DFS time in the ITT KRAS wild-type population	3-years DFS
Secondary	Overall survival		5 years