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

• ClinicalTrials.gov Identifier: NCT00958737
• Recruitment Status: Unknown
• First Posted: August 13, 2009
• Last Update Posted: March 1, 2017
• 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: March 1, 2017
• Study Start Date: April 2009
• Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 6, 2012): Disease-free survival (defined as local, regional, or distant relapse; second primary colorectal cancer; or death from any cause) [ Time Frame: 3 years after randomisation ]
• 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)
• Change History: Complete list of historical versions of study NCT00958737 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: November 6, 2012)

• Overall survival [ Time Frame: death from randomization ]
• Toxicity according to NCI CTCAE version 3.0 [ Time Frame: each cycle ]
• Total cumulative dose received vs planned dose [ Time Frame: at the end of treatment ]
• Incidence and timing of dose reductions and/or modifications of time [ Time Frame: at the end of treatment ]

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
  Given IV
• Drug: fluorouracil
  Given IV
• Drug: leucovorin calcium
  Given IV
• Drug: oxaliplatin
  Given IV
• Drug: XELOX regimen
• Drug: Capecitabine
  oral

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

  • Drug: FOLFOX regimen
  • Drug: fluorouracil
  • Drug: leucovorin calcium
  • Drug: oxaliplatin
  • Drug: XELOX regimen
  • Drug: Capecitabine

• Publications *: André 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, Fédération Française de Cancérologie 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 12, 2009): 2000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2017
• Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colon cancer

  • Tumor location > 12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery (high rectum)
  • AJCC/UICC stage III disease
  • Adenocarcinoma
  • No evidence of metastatic disease (including presence of tumor cells in ascites or peritoneal carcinomatosis resected "en bloc")

• Undergone curative surgery for colon cancer within the past 8 weeks

  • No gross, macroscopic, or microscopic evidence of residual disease (R1 or R2 resections) after surgery
• Carcinoembryonic antigen ≤ 10 ng/mL (2 times normal)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and up to 1 month after completion of study treatment
• Willing and able to comply with study requirements
• No clinically relevant cardiovascular disease (ischemic myocardial infarction in the past year and/or unstable ischemic cardiopathy)
• No other malignancies within the past 5 years except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
• No history or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ CTCAE v.3.0 grade 1
• No known hypersensitivity reaction to any of the components of study treatments
• Registered in a national health care system (CMU included)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 28 days since prior treatment, no concurrent treatment, and no treatment while the patient is disease-free during study follow-up with another investigational drug
• No concurrent treatment or treatment while the patient is disease-free during study follow-up with other cytotoxic agents, or active or passive immunotherapy for colon cancer

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (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: CDR0000647466; FRE-GERCOR-C09-1-IDEA; EUDRACT-2009-010384-16; EU-20957
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: GERCOR - Multidisciplinary Oncology Cooperative Group
• Study Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Collaborators: Not Provided

Investigators

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

• PRS Account: GERCOR - Multidisciplinary Oncology Cooperative Group
• Verification Date: January 2017