Colon Cancer (High-risk Stage III: pT4N1 or pT1 to 4 N2) Clinical Trial
— IROCASOfficial title:
A Phase III, Randomised, International Trial Comparing mFOLFIRINOX Triplet Chemotherapy to mFOLFOX for High-risk Stage III Colon Cancer in Adjuvant Setting
| Verified date | August 2023 |
| Source | UNICANCER |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 792 |
| Est. completion date | June 2027 |
| Est. primary completion date | June 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | 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 ß-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 |
| Country | Name | City | State |
|---|---|---|---|
| Canada | 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 | Montréal | Quebec |
| Canada | Allan Blair Cancer Centre | Regina | Saskatchewan |
| France | 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 | Hôpital privé Jean Mermoz | Lyon | |
| France | Hospices civils de Lyon - Hôpital Edouard Herriot | 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 Gregoire | |
| France | Clinique de la Côte d'Emeraude | Saint-Malo |
| Lead Sponsor | Collaborator |
|---|---|
| UNICANCER | Canadian Cancer Trials Group, GONO GROUP |
Canada, France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Disease Free Survival | 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. |
2 YEARS after inclusion | |
| Secondary | Overall Survival | Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death from any cause | 5 YEARS after inclusion | |
| Secondary | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Safety of the study treatment will be assessed on occurrence of Adverse Events (AEs), intake of concomitant treatments, per-treatment arising changes in physical examination, vital signs (blood pressure, pulse rate and body temperature), ECG, and clinical laboratory tests (biochemistry, haematology). Safety parameters will be graded based on NCI CTCAE v4.03 classification.
The following parameters will be particularly followed: The incidence of haematological toxicities (grade 3-4, in particular neutropenia and febrile neutropenia); The incidence of GI toxicities, in particular diarrhea; The incidence of peripheral neuropathy. |
2 YEARS after inclusion |