IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting

NCT02967289 | Completed Phase 3 DMC

• 2 other identifiers: UC-0110/1609_PRODIGE52/UCGI292016-001491-29
• Study Type: interventional
• Target: 792
• Locations: 2 countries
• Sites: 17

Brief Summary

The trial is a phase III, multicenter, open-labeled randomized trial comparing the association of 5-fluorouracil (5-FU), folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) versus oxaliplatin, folinic acid, and 5-FU (mFOLFOX 6) chemotherapy protocols in patients with high-risk stage III colon cancer in the adjuvant setting.

Conditions

Colon Cancer (High-risk Stage III: pT4N1 or pT1 to 4 N2)

Keywords

colon; cancer; stage 3; high-risk; mFolfirinox; mFolfox6; adjuvant

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival (DFS)

  DFS : defined as the time from the date of randomization up to the date of: * first local, regional or distant relapse; * second colorectal cancer; * death from any cause included treatment-related death.

  3 YEARS after inclusion

Secondary Outcomes (3)

• Disease Free Survival

  2 YEARS after inclusion

• Overall Survival

  5 YEARS after inclusion

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  2 YEARS after inclusion

Study Arms (2)

Arm A

EXPERIMENTAL

mFOLFIRINOX Folfox Protocol + Irinotecan

Drug: Irinotecan; Drug: Folfox Protocol

Arm B

ACTIVE COMPARATOR

mFOLFOX 6 Folfox Protocol

Drug: Folfox Protocol

Interventions

Irinotecan DRUG

every 14 days, 12 cycles, 24 weeks, new cycle beginning on day 15: irinotecan (Campto®) 180 mg/m² on D1, IV infusion over 90 minutes to begin 30 min after folinic acid infusion is started

Also known as: Campto

Arm A

Folfox Protocol DRUG

every 14 days, 12 cycles, 24 weeks, new cycle beginning on day 15: oxaliplatin (Eloxatin®) 85 mg/m² on D1, IV infusion over 2 hours, followed by folinic acid 400 mg/m² (racemic mixture) (or 200 mg/m² if L-folinic acid) IV infusion over 2 hours 5-FU 2400 mg/m²/h IV continuous infusion over 46 hours starting at the end of folinic acid infusion

Also known as: acid folinic + oxaliplatine + 5-FU

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient ≥18 years and \< 75 years
• Patient ≥18 years and \<71 years must have an ECOG ≤1 - Patients ≥71 years and \< 75 years must have an ECOG = 0
• Pathologically confirmed high-risk stage III colon adenocarcinoma, restricted to pT4N1 or pT1-4N2 tumor.
• Curative R0 surgical resection.
• 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
• Start of study drug treatment has to be performed less than 56 days after surgery.
• No prior chemotherapy.
• No prior abdominal or pelvic irradiation.
• Patient with adequate organ function:
• Absolute neutrophil count (ANC) ≥ 2 x 109/L
• Haemoglobin ≥9 g/dL
• Platelets (PTL) ≥100 x 109/L
• AST/ALT ≤2.5 x ULN
• Alkaline phosphatase ≤2.5 x ULN
• Total Bilirubin ≤1.5 x ULN (Upper Limit of Normal)

You may not qualify if:

• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start. Incompletely healed wounds or anticipation of the need for major surgical procedure during the course of the study
• Metastatic disease
• Presence of inflammatory bowel disease and/or ileus
• Known hypersensitivity reaction to any of the components of study treatments.
• Pregnancy (absence to be confirmed by β-hCG test) or breast-feeding period
• Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia (for men: QTc ≥450 msec, for women: QTc ≥470 msec)
• Previous malignancy in the last 5 years except curative treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
• Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent
• History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1 Common Toxicity Criteria for Adverse Events (CTCAE) v4.03.
• Any significant disease which, in the investigator's opinion, would exclude the patient from the study.
• Patient with a DPD deficiency or UGT1A1 homozygous 7/7; the test should be done for all patients before 5-FU administration, according to ANSM communication regarding recommendation about high risk of no testing DPD in patient before 5-FU administration; (Appendices 8 to 11).
• Patients already included in another therapeutic trial involving an experimental drug

Sponsors & Collaborators

• UNICANCER: lead
• Canadian Cancer Trials Group: collaborator
• GONO GROUP: collaborator

Study Sites (17)

The PEI Cancer Treatment Centre Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

Location

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Location

Institut de Cancérologie de l'Ouest -site Paul Papin

Angers, France

Location

CHD de Vendée

La Roche-sur-Yon, France

Location

Ch Emile Roux

Le Puy-en-Velay, France

Location

Hospices civils de Lyon - Hôpital Edouard Herriot

Lyon, France

Location

Hôpital privé Jean Mermoz

Lyon, France

Location

Icm Val D'Aurelle

Montpellier, France

Location

Institut de Cancérologie de l'Ouest -site René Gauducheau

Nantes, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

Centre Hospitalier Annecy Genevois

Pringy, France

Location

Institut Jean Godinot

Reims, France

Location

CHP Saint Grégoire

Saint-Grégoire, France

Location

Clinique de la Côte d'Emeraude

St-Malo, France

Location

Related Publications (1)

• Bennouna J, Andre T, Campion L, Hiret S, Miglianico L, Mineur L, Touchefeu Y, Artru P, Asmis T, Bouche O, Borde F, Kavan P, Lam YH, Rajpar LS, Emile JF, Jouffroy C, Gill S, Taieb J. Rationale and Design of the IROCAS Study: Multicenter, International, Randomized Phase 3 Trial Comparing Adjuvant Modified (m) FOLFIRINOX to mFOLFOX6 in Patients With High-Risk Stage III (pT4 and/or N2) Colon Cancer-A UNICANCER GI-PRODIGE Trial. Clin Colorectal Cancer. 2019 Mar;18(1):e69-e73. doi: 10.1016/j.clcc.2018.09.011. Epub 2018 Oct 19.

  PMID: 30415988 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Neoplasms

Interventions

Irinotecan; Folfox protocol; Leucovorin; Oxaliplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jaafar BENNOUNA, Professor

  Hôpital FOCH, SURESNES

  STUDY CHAIR

• Julien TAIEB, Professor

  Hôpital Européen Georges-Pompidou, PARIS

  STUDY CHAIR

• Thierry ANDRE, Professor

  AP-HP Hôpital Saint-Antoine, PARIS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The primary end-point is the Disease Free Survival (DFS) at 3 years, defined as the time from the date of randomization up to the date of: * first local, regional or distant relapse; * second colorectal cancer; * death from any cause included treatment-related death. Other primary cancer (except second primary colorectal) will be ignored. Second primary cancer will be recorded to have the opportunity of evaluating other definition of DFS.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The trial is a phase III, multicenter, open-labeled randomized trial comparing the association 5-fluorouracil, folinic acid, irinotecan and oxaliplatin (mFOLFIRINOX) versus oxaliplatin, folinic acid, 5FU (mFOLFOX 6) chemotherapy protocols in patients with high-risk stage III colon cancer in the adjuvant setting.

Study Record Dates

• First Submitted: November 9, 2016
• First Posted: November 18, 2016
• Study Start: March 27, 2017
• Primary Completion: June 15, 2025
• Study Completion: July 15, 2025
• Last Updated: November 17, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

Locations

FR (13); CA (4)