Combination Chemotherapy for 3 Months or 6 Months in Treating Patients With Stage III Colon Cancer (IDEA)

• ClinicalTrials.gov Identifier: NCT00958737
• Recruitment Status: Active, not recruiting
• First Posted: August 13, 2009
• Last Update Posted: September 29, 2023
• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Information provided by (Responsible Party): GERCOR - Multidisciplinary Oncology Cooperative Group

Tracking Information

• First Submitted Date: August 12, 2009
• First Posted Date: August 13, 2009
• Last Update Posted Date: September 29, 2023
• Actual Study Start Date: May 12, 2009
• Actual Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2023)

Disease-free survival (DFS) [ Time Frame: 3 years after randomisation ]

DFS, defined as the time from random assignment to relapse or death, whichever occurred first. Secondary colorectal cancers were regarded as DFS events, whereas noncolorectal cancers were disregarded in the analysis.

• Original Primary Outcome Measures (submitted: August 12, 2009): Disease-free survival (defined as local, regional, or distant relapse; second primary colorectal cancer; or death from any cause)

Current Secondary Outcome Measures (submitted: September 27, 2023)

• Overall survival (OS) [ Time Frame: Death from randomization; up to 7 years after randomization ]
  The time from the date of randomization to the date of death from any cause
• Safety profile [ Time Frame: Assessed up to 6 months after randomisation ]
  All grade and severe toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
• Treatment compliance [ Time Frame: Until 3 months or 6 months (according randomization arm) ]
  duration, dose intensity, and dose in mg/m2

Original Secondary Outcome Measures (submitted: August 12, 2009)

• Overall survival
• Toxicity according to NCI CTCAE version 3.0
• Frequency and nature of adverse events and serious adverse events
• Total cumulative dose received vs planned dose
• Incidence and timing of dose reductions and/or modifications of time
• Premature withdrawals

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Combination Chemotherapy for 3 Months or 6 Months in Treating Patients With Stage III Colon Cancer
• Official Title: A Phase III Randomized Trial Investigating the Duration of Adjuvant Therapy(3 Versus 6 Months) With the Modified FOLFOX 6 or XELOX Regimens for Patients With Stage III Colon Cancer

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving more than one drug (combination chemotherapy) is more effective when given for 3 months or 6 months in treating patients with colon cancer.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy for 3 months to see how well it works compared with giving combination chemotherapy for 6 months in treating patients with stage III colon cancer.

Detailed Description

OBJECTIVES:

Primary Objective

• To assess whether a 3-month modified FOLFOX 6 or XELOX treatment is not inferior to a 6-month modified FOLFOX 6 or XELOX treatment in terms of disease free survival (DFS) in patients with radically resected stage III colon cancer.

Secondary Objectives

• To assess whether 3-month modified FOLFOX 6 (6 cycles) or XELOX (4 cycles) treatment is not inferior to 6-month modified FOLFOX 6 (12 cycles) or XELOX (8 cycles) treatment in terms of overall survival (OS) in patients with radically resected stage III colon cancer
• To evaluate the safety profiles of the treatment groups

Tertiary Objectives

• For patients who signed a specific informed consent, blood and tumour tissue samples will be stored, registered, and centralized in a data bank for translational research projects that will be further determined according to the literature and scientific knowledge at the time of the end of inclusion. (exploratory)
• An economic evaluation at the country level will be conducted alongside the clinical evaluation. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to center, T stage (1 or 2 vs 3 vs 4), N stage (1 vs 2), performance status (0 vs 1 vs 2), and age (< 70 years vs ≥ 70 years). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive modified FOLFOX 6 comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Treatment repeats every 14 days for 6 courses (3 months).
• Arm II: Patients receive modified FOLFOX 6 as in arm I. Treatment repeats every 14 days for 12 courses (6 months).

Blood and tumor samples may be collected at baseline for pharmacogenetic and other analyses.

After completion of study treatment, patients are followed up every 6 months for 8 years.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: FOLFOX regimen
  6 or 12 treatments of FOLFOX (FOLFOX4 or modified FOLFOX6 (mFOLFOX6))
  Other Name: folinic acid, infusional fluorouracil, and oxaliplatin
• Drug: CAPOX
  4 or 8 cycles
  Other Name: capecitabine plus oxaliplatin; XELOX

Study Arms

• Experimental: Arm I

  Patients receive modified FOLFOX 6 comprising oxaliplatin IV 85 mg/m² over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Treatment repeats every 14 days for 6 courses (3 months).

  Patients receive CAPOX comprising oxaliplatin IV 130 mg/m² over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which will be administered orally at a dose of 1000 mg/m2 twice-daily (equivalent to a total daily dose of 2000 mg/m2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment)

  Interventions:

  • Drug: FOLFOX regimen
  • Drug: CAPOX
• Experimental: Arm II
  Patients receive modified FOLFOX 6 or CAPOX as in arm I. Treatment repeats every 14 days for 12 courses (6 months)or regarding CAPOX every 21 days for 8 courses (6 month).
  Interventions:

  • Drug: FOLFOX regimen
  • Drug: CAPOX

Publications *

• Andre T, Vernerey D, Mineur L, Bennouna J, Desrame J, Faroux R, Fratte S, Hug de Larauze M, Paget-Bailly S, Chibaudel B, Bez J, Dauba J, Louvet C, Lepere C, Dupuis O, Becouarn Y, Mabro M, Egreteau J, Bouche O, Deplanque G, Ychou M, Galais MP, Ghiringhelli F, Dourthe LM, Bachet JB, Khalil A, Bonnetain F, de Gramont A, Taieb J; for PRODIGE investigators, GERCOR, Federation Francaise de Cancerologie Digestive, and UNICANCER. Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial. J Clin Oncol. 2018 May 20;36(15):1469-1477. doi: 10.1200/JCO.2017.76.0355. Epub 2018 Apr 5.
• 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.
• Delattre JF, Cohen R, Henriques J, Falcoz A, Emile JF, Fratte S, Chibaudel B, Dauba J, Dupuis O, Becouarn Y, Bibeau F, Taieb J, Louvet C, Vernerey D, Andre T, Svrcek M. Prognostic Value of Tumor Deposits for Disease-Free Survival in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the IDEA France Phase III Trial (PRODIGE-GERCOR). J Clin Oncol. 2020 May 20;38(15):1702-1710. doi: 10.1200/JCO.19.01960. Epub 2020 Mar 13.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 12, 2009): 2000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Actual Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• Patients who have undergone surgery for colon cancer, defined as a tumor location >12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery (high rectum), without gross or microscopic evidence of residual disease after surgery with curative intent.
• Histologically confirmed AJCC/UICC stage III adenocarcinoma colon cancer.
• Age >18 years.
• Curative surgery and no more than 8 weeks prior to randomization.
• ECOG performance Status (ECOG-PS) <2.
• Signed written informed consent obtained prior to any study specific procedures.
• CEA ≤ 10 ng/ml (2 X normal value).
• Post-menopausal women or women willing to accept the use of an effective contraceptive regimen during the treatment period and up to 1 month after the end of the study treatment. All non postmenopausal women should have a negative pregnancy test within 72 hours prior to randomization. Men should accept to use an effective contraception during the treatment period, and up to 1 month after the end of the study treatment.
• Registration in a national health care system (CMU included).

Exclusion criteria:

Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in ascites or peritoneal carcinomatosis resected "en bloc").

• Cancer of low or medium rectum with tumor location < 12 cm from the anal verge by endoscopy.
• 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).
• Pregnant or lactating women
• Clinically relevant cardiovascular disease (for example: ischemic myocardial infarction in the last year and/or unstable ischemic cardiopathy).
• History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1 Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0.
• Known hypersensitivity reaction to any of the components of study treatments.
• Current or recent (within 28 days prior to randomization) treatment with another investigational drug.
• Subject unwilling or unable to comply with study requirements.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00958737
• Other Study ID Numbers: IDEA-C09-1; 2009-010384-16 ( EudraCT Number ); EU-20957 ( Other Identifier: EU Clinical Trials Register )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: GERCOR - Multidisciplinary Oncology Cooperative Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Thierry Andre, MD; GERCOR - Multidisciplinary Oncology Cooperative Group

• PRS Account: GERCOR - Multidisciplinary Oncology Cooperative Group
• Verification Date: September 2023