Clinical trial NCT02967289: IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting
Official title: A Phase III, Randomised, International Trial Comparing mFOLFIRINOX Triplet Chemotherapy to mFOLFOX for High-risk Stage III Colon Cancer in Adjuvant Setting
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Colon Cancer (High-risk Stage III: pT4N1 or pT1 to 4 N2)
Keywords: colon
cancer
stage 3
high-risk
mFolfirinox
mFolfox6
adjuvant
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Trials Group
name: GONO GROUP
First posted: 2016-11-18
Enrollment: 792
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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

Eligibility criteria: DIAGNOSIS AND 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

Primary outcomes:
measure: Disease Free Survival (DFS)
timeFrame: 3 YEARS after inclusion
Secondary outcomes:
measure: Disease Free Survival
timeFrame: 2 YEARS after inclusion
measure: Overall Survival
timeFrame: 5 YEARS after inclusion
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 2 YEARS after inclusion
Other outcomes:
Locations:
city: Charlottetown
country: Canada
facility: The PEI Cancer Treatment Centre Queen Elizabeth Hospital
state: Prince Edward Island
city: Greenfield Park
country: Canada
facility: Hopital Charles LeMoyne
state: Quebec
city: Montréal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest -site Paul Papin
city: La Roche-sur-Yon
country: France
facility: CHD de Vendée
city: Le Puy-en-Velay
country: France
facility: Ch Emile Roux
city: Lyon
country: France
facility: Hospices civils de Lyon - Hôpital Edouard Herriot
city: Lyon
country: France
facility: Hôpital privé Jean Mermoz
city: Montpellier
country: France
facility: Icm Val D'Aurelle
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest -site René Gauducheau
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Pringy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Reims
country: France
facility: Institut Jean Godinot
city: Saint Gregoire
country: France
facility: CHP Saint Grégoire
city: Saint-Malo
country: France
facility: Clinique de la Côte d'Emeraude
Study officials:
affiliation: Hôpital FOCH, SURESNES
name: Jaafar BENNOUNA, Professor
role: STUDY_CHAIR
affiliation: Hôpital Européen Georges-Pompidou, PARIS
name: Julien TAIEB, Professor
role: STUDY_CHAIR
affiliation: AP-HP Hôpital Saint-Antoine, PARIS
name: Thierry ANDRE, Professor
role: STUDY_CHAIR
References:
citation: 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.