Phase III Randomized Trial of mFOLFIRINOX Versus mFOLFOX in Adjuvant Treatment of High-Risk Stage III Colon Cancer
- Trial ID
- 2024-517489-41-00
- Protocol
- UC-0110/1609
- Sponsor
- Unicancer
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **3-year Disease-Free Survival** rate in patients with high-risk stage III colon cancer. This measure is clinically significant as it provides insight into the effectiveness of the treatment in preventing cancer recurrence over a substantial period, which is crucial for long-term patient outcomes.
Secondary objectives include:
- Evaluation of Efficacy: **Disease-free Survival** at 2 years, which helps in understanding the short-term effectiveness of the treatment.
- **Overall Survival (OS)**, which is a critical endpoint reflecting the ultimate benefit of the treatment in extending life.
- Evaluation of **Toxicity**, which is essential for determining the safety profile of the treatment regimen.
Participants
The clinical trial involves a total of **20 participants** diagnosed with **high-risk stage III colon cancer**. The study population includes both male and female subjects, aged between 18 and 74 years. Participants were selected based on specific criteria, including a pathologically confirmed diagnosis of high-risk stage III colon adenocarcinoma, and having undergone curative R0 surgical resection. The trial population is characterized by a life expectancy of at least five years and adequate organ function. Participants must not have received prior chemotherapy or abdominal/pelvic irradiation. Lifestyle considerations such as adequate contraception are required if applicable. The trial includes individuals with public or private health insurance coverage and those who are able and willing to comply with study procedures. The study does not specifically exclude vulnerable populations, indicating a broad inclusion approach within the defined criteria.
Plans and Procedures
The clinical trial is a **Phase III** study designed to evaluate the efficacy and safety of mFOLFIRINOX triplet chemotherapy compared to mFOLFOX in patients with high-risk stage III colon cancer in an adjuvant setting. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The primary objective is to assess the 3-year **Disease Free Survival** (DFS) rate, with secondary endpoints including 2-year DFS, overall survival, and evaluation of treatment-related toxicity. The trial is expected to conclude by May 2026, with recruitment having commenced in March 2017.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, health status, and previous treatments. Following successful screening, participants will be randomized to receive either the mFOLFIRINOX or mFOLFOX regimen. The treatment period is set for a maximum of two cycles, with each cycle lasting two weeks. Study visits will include regular follow-up assessments to monitor the efficacy and safety of the treatment, including physical examinations, laboratory tests, and imaging studies as necessary. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
Participant involvement is expected to last for the duration of the treatment cycles, with additional follow-up visits scheduled to assess long-term outcomes. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, withdrawal of consent, or any significant protocol deviations. The study will adhere to strict ethical guidelines, ensuring that all participants provide informed consent and that their safety and well-being are prioritized throughout the trial.
Treatment
The clinical trial involves the administration of **oxaliplatin**, a **solution for infusion**. This experimental medication is administered **intravenously** at a dosage of **85 mg/m²**. The treatment is scheduled to be administered once every two weeks, with a maximum treatment period of two cycles. The active substance, oxaliplatin, is of chemical origin and is not formulated for pediatric use. Participant compliance with the dosing schedule will be monitored throughout the trial.
**Folinic acid** is also utilized in this study as a **solution for injection**. It is administered **intravenously** at a dosage of **400 mg/m²**. Similar to oxaliplatin, folinic acid is given once every two weeks, with a maximum treatment period of two cycles. The active substance is chemically derived, and the formulation is not intended for pediatric patients. Compliance with the administration schedule will be closely monitored.
The trial further includes the use of **fluorouracil**, provided as a **concentrate for solution for injection/infusion**. This medication is administered **intravenously** at a dosage of **2400 mg/m²**. The administration follows a bi-weekly schedule, with a maximum treatment period of two cycles. The active substance is of chemical origin, and the formulation is not suitable for pediatric use. Participant adherence to the dosing regimen will be assessed throughout the study.
Additionally, **irinotecan** is employed in the trial as a **concentrate for solution for infusion**. It is administered **intravenously** at a dosage of **180 mg/m²**. The treatment is scheduled bi-weekly, with a maximum treatment period of two cycles. The active substance is chemically derived, and the formulation is not designed for pediatric use. Monitoring of participant compliance with the dosing schedule is an integral part of the trial protocol.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the measurement of **Disease Free Survival (DFS)** at 3 years. DFS is defined as the time from the date of randomization to the date of first local, regional, or distant relapse, second colorectal cancer, or death from any cause, including treatment-related death. Other primary cancers, except for a second primary colorectal cancer, will be ignored in this assessment. The secondary efficacy endpoint includes DFS at 2 years, which follows the same definition as the primary endpoint but over a shorter duration.
Additionally, **Overall Survival (OS)** will be evaluated as a secondary endpoint. OS is defined as the time from the date of randomization to the date of documented death from any cause. The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to ensure comprehensive assessment of the treatment's impact on patient outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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) - Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula) - Kalemia, magnesemia, calcemia ≥ 1 LLN (Lower Limit of Normal) - Carcinoembryogenic antigen (CEA) ≤10ng/mL after surgery (during screening period)
- Adequate contraception if applicable.
- Patient able and willing to comply with study procedures as per protocol
- 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
- Public or private health insurance coverage
- Life expectancy of > or = at 5 years
- Uracilemia < 16 ng/ml (only for french centers)
Exclusion Criteria
- 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;
- Patients already included in another therapeutic trial involving an experimental drug
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 27 Mar 2017 | 50 |
 Italy | Not Recruiting | 27 Mar 2017 | 16 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
OXALIPLATIN | Test | — | INTRAVENOUS | 85 | 2 | SUB09490MIG |
FOLINIC ACID | Test | — | INTRAVENOUS | 400 | 2 | SUB13910MIG |
IRINOTECAN | Test | — | INTRAVENOUS | 180 | 2 | SUB08295MIG |
FLUOROURACIL | Test | — | INTRAVENOUS | 2400 | 2 | SUB07721MIG |