IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting

NCT ID: NCT02967289

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 792 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-27
• Study Completion Date: 2025-07-15

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.

Detailed Description

After inclusion and non-inclusion criteria have been fulfilled and the patient consent has been obtained, the patient will be included and randomized in the trial. The maximum delay allowed between the signature of the consent form by the patient and the randomization in the study is 28 days.

The randomization procedure using minimization method will allocate the treatments mFOLFIRINOX or mFOLFOX 6 with a 1:1 ratio, and will be stratified by the following criteria:

• Perforation or urgent surgery versus no perforation and no urgent surgery.
• T1-T3N2 vs T4aN1 versus T4bN1 versus T4N2.
• Right colon (right of splenic flexure) vs left colon.
• Country (France vs Canada vs Italy). Patient eligible and who have signed the informed consent will be randomized in one of the two treatments arms and will receive every 14 days their treatment for a duration of 12 cycles.

Arm A: mFOLFIRINOX Arm B: mFOLFOX 6

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

mFOLFIRINOX Folfox Protocol + Irinotecan

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: 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

Folfox Protocol

Intervention Type: 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

Arm B

mFOLFOX 6 Folfox Protocol

Group Type: ACTIVE_COMPARATOR

Folfox Protocol

Intervention Type: 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

Interventions

Irinotecan

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

Intervention Type: DRUG

Folfox Protocol

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

Intervention Type: DRUG

Other Intervention Names

Campto; acid folinic + oxaliplatine + 5-FU

Eligibility Criteria

Inclusion Criteria

1. Patient ≥18 years and < 75 years

2. Patient ≥18 years and <71 years must have an ECOG ≤1 - Patients ≥71 years and < 75 years must have an ECOG = 0

3. Pathologically confirmed high-risk stage III colon adenocarcinoma, restricted to pT4N1 or pT1-4N2 tumor.

4. Curative R0 surgical resection.

5. 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

6. Start of study drug treatment has to be performed less than 56 days after surgery.

7. No prior chemotherapy.

8. No prior abdominal or pelvic irradiation.

9. 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)
• Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)
• Kalemia, magnesemia, calcemia ≥ 1 LLN (Lower Limit of Normal)
• Carcinoembryonic antigen (CEA) ≤10ng/mL after surgery (during screening period)

10. Adequate contraception if applicable.

11. Patient able and willing to comply with study procedures as per protocol

12. Patient able to understand and willing to sign and date the written voluntary informed consent form at screening visit prior to any protocol-specific procedures

13. Public or private health insurance coverage

14. Life expectancy of > or = at 5 years

15. Uracilemia < 16 ng/ml (only for french centers)

Exclusion Criteria

1. 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

2. Metastatic disease

3. Presence of inflammatory bowel disease and/or ileus

4. Known hypersensitivity reaction to any of the components of study treatments.

5. Pregnancy (absence to be confirmed by β-hCG test) or breast-feeding period

6. 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)

7. Previous malignancy in the last 5 years except curative treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix

8. Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent

9. 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.

10. Any significant disease which, in the investigator's opinion, would exclude the patient from the study.

11. 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).

12. Patients already included in another therapeutic trial involving an experimental drug

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Canadian Cancer Trials Group

NETWORK

Sponsor Role: collaborator

GONO GROUP

UNKNOWN

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaafar BENNOUNA, Professor

Role: STUDY_CHAIR

Hôpital FOCH, SURESNES

Julien TAIEB, Professor

Role: STUDY_CHAIR

Hôpital Européen Georges-Pompidou, PARIS

Thierry ANDRE, Professor

Role: STUDY_CHAIR

AP-HP Hôpital Saint-Antoine, PARIS

Locations

The PEI Cancer Treatment Centre Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Institut de Cancérologie de l'Ouest -site Paul Papin

Angers, , France

CHD de Vendée

La Roche-sur-Yon, , France

Ch Emile Roux

Le Puy-en-Velay, , France

Hospices civils de Lyon - Hôpital Edouard Herriot

Lyon, , France

Hôpital privé Jean Mermoz

Lyon, , France

Icm Val D'Aurelle

Montpellier, , France

Institut de Cancérologie de l'Ouest -site René Gauducheau

Nantes, , France

Hôpital Européen Georges Pompidou

Paris, , France

Hôpital Saint Antoine

Paris, , France

Centre Hospitalier Annecy Genevois

Pringy, , France

Institut Jean Godinot

Reims, , France

CHP Saint Grégoire

Saint-Grégoire, , France

Clinique de la Côte d'Emeraude

St-Malo, , France

Countries

Canada; France

References

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.

Reference Type: DERIVED

PMID: 30415988 (View on PubMed)

Other Identifiers

2016-001491-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UC-0110/1609_PRODIGE52/UCGI29

Identifier Type: -

Identifier Source: org_study_id