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

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Folfox
Cetuximab
Sponsored by
Federation Francophone de Cancerologie Digestive
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage III colon cancer, adenocarcinoma of the colon

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital Duffaut
  • CHU de Caen
  • Hopital Robert Boulin
  • Hopital Bichat - Claude Bernard
  • CHU Pitie-Salpetriere
  • Hopital Tenon
  • Centre Hospitalier Yves Le Foll
  • Nouvelle Clinique Generale

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Folfox+Cetuximab

Folfox

Arm Description

FOLFOX-4 Cetuximab alone every 2 weeks

FOLFOX-4 alone every 2 weeks

Outcomes

Primary Outcome Measures

Disease-free survival
DFS time in the ITT KRAS wild-type population

Secondary Outcome Measures

Overall survival

Full Information

First Posted
December 14, 2005
Last Updated
November 5, 2020
Sponsor
Federation Francophone de Cancerologie Digestive
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1. Study Identification

Unique Protocol Identification Number
NCT00265811
Brief Title
Combination Chemotherapy With or Without Cetuximab in Treating Patients With Stage III Colon Cancer That Was Completely Removed By Surgery
Official Title
Adjuvant Treatment of Fully Resected Stage III Colon Cancer With FOLFOX-4 Versus FOLFOX-4 Plus Cetuximab
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
November 2005 (Actual)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
June 22, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Federation Francophone de Cancerologie Digestive

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
stage III colon cancer, adenocarcinoma of the colon

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2559 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Folfox+Cetuximab
Arm Type
Experimental
Arm Description
FOLFOX-4 Cetuximab alone every 2 weeks
Arm Title
Folfox
Arm Type
Active Comparator
Arm Description
FOLFOX-4 alone every 2 weeks
Intervention Type
Drug
Intervention Name(s)
Folfox
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Primary Outcome Measure Information:
Title
Disease-free survival
Description
DFS time in the ITT KRAS wild-type population
Time Frame
3-years DFS
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julien Taieb, MD
Organizational Affiliation
CHU Pitie-Salpetriere
Official's Role
Study Chair
Facility Information:
Facility Name
Hopital Duffaut
City
Avignon
ZIP/Postal Code
84902
Country
France
Facility Name
CHU de Caen
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Hopital Robert Boulin
City
Libourne
ZIP/Postal Code
33500
Country
France
Facility Name
Hopital Bichat - Claude Bernard
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
CHU Pitie-Salpetriere
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Hopital Tenon
City
Paris
ZIP/Postal Code
75970
Country
France
Facility Name
Centre Hospitalier Yves Le Foll
City
Saint Brieuc Cedex 1
ZIP/Postal Code
BP 2367
Country
France
Facility Name
Nouvelle Clinique Generale
City
Valence
ZIP/Postal Code
26000
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
18279058
Citation
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.
Results Reference
result
PubMed Identifier
24928083
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, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Jul;15(8):862-73. doi: 10.1016/S1470-2045(14)70227-X. Epub 2014 Jun 11.
Results Reference
result
PubMed Identifier
36306483
Citation
Gallois C, Shi Q, Meyers JP, Iveson T, Alberts SR, de Gramont A, Sobrero AF, Haller DG, Oki E, Shields AF, Goldberg RM, Kerr R, Lonardi S, Yothers G, Kelly C, Boukovinas I, Labianca R, Sinicrope FA, Souglakos I, Yoshino T, Meyerhardt JA, Andre T, Papamichael D, Taieb J. Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials. J Clin Oncol. 2023 Feb 1;41(4):803-815. doi: 10.1200/JCO.21.02726. Epub 2022 Oct 28.
Results Reference
derived
PubMed Identifier
33356421
Citation
Cohen R, Taieb J, Fiskum J, Yothers G, Goldberg R, Yoshino T, Alberts S, Allegra C, de Gramont A, Seitz JF, O'Connell M, Haller D, Wolmark N, Erlichman C, Zaniboni A, Lonardi S, Kerr R, Grothey A, Sinicrope FA, Andre T, Shi Q. Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials. J Clin Oncol. 2021 Feb 20;39(6):642-651. doi: 10.1200/JCO.20.01600. Epub 2020 Dec 23.
Results Reference
derived
PubMed Identifier
32085892
Citation
Salem ME, Yin J, Goldberg RM, Pederson LD, Wolmark N, Alberts SR, Taieb J, Marshall JL, Lonardi S, Yoshino T, Kerr RS, Yothers G, Grothey A, Andre T, De Gramont A, Shi Q. Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database. Ann Oncol. 2020 Apr;31(4):480-486. doi: 10.1016/j.annonc.2019.12.007. Epub 2020 Jan 16.
Results Reference
derived
PubMed Identifier
31268130
Citation
Taieb J, Shi Q, Pederson L, Alberts S, Wolmark N, Van Cutsem E, de Gramont A, Kerr R, Grothey A, Lonardi S, Yoshino T, Yothers G, Sinicrope FA, Zaanan A, Andre T. Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies. Ann Oncol. 2019 Sep 1;30(9):1466-1471. doi: 10.1093/annonc/mdz208.
Results Reference
derived

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

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