Evaluation of Circulating Tumor DNA-Guided Adjuvant Therapy with Fluorouracil, Folinic Acid, and Oxaliplatin in Stage II Colon Carcinoma
- Trial ID
- 2024-515297-27-00
- Protocol
- PRODIGE 70
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to improve **Disease Free Survival (DFS)** in patients with centralized circulating tumor DNA (ctDNA) positive colon carcinoma by administering FOLFOX6m adjuvant treatment. This objective is clinically relevant as enhancing DFS can potentially lead to better long-term outcomes and reduce the risk of cancer recurrence in this patient population.
Secondary objectives include:
- Improving Time to Recurrence (TTR) and Overall Survival (OS) in ctDNA positive patients with adjuvant therapy compared to those without therapy.
- Comparing DFS and OS in ctDNA positive versus ctDNA negative patients without adjuvant treatment.
- Estimating toxicities using the NCI-CTC v4 classification in ctDNA positive patients with or without adjuvant therapy to assess treatment tolerability.
- Improving the success rate of prognostication in stage II colorectal cancer by evaluating the added value of ctDNA on classical prognostic factors.
- Identifying biological factors predictive of adjuvant treatment efficacy in ctDNA positive stage II colorectal cancer.
Participants
The clinical trial focuses on patients diagnosed with **colon carcinoma**, specifically targeting those with histologically confirmed stage II colon and high rectum adenocarcinoma. The study population includes both male and female participants aged between 18 and 80 years. Participants are required to have a life expectancy of at least 5 years and must demonstrate adequate hematological and organ function. The trial does not include a vulnerable population. Participants were selected based on specific inclusion criteria, such as no prior chemotherapy or irradiation for colorectal cancer, and no evidence of metastatic disease. The sponsor has not provided the total number of participants involved in the trial. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to improve Disease Free Survival (DFS) in patients who are centralized ctDNA positive through the administration of FOLFOX6m adjuvant treatment.
Plans and Procedures
The clinical trial is a **randomized**, **controlled**, and **double-blind** study designed to evaluate the efficacy of adjuvant chemotherapy in patients with stage II **colon carcinoma**. The primary objective is to improve the 3-year Disease-Free Survival (DFS) from 25% to 42.5% in patients who are positive for circulating tumor DNA (ctDNA) by administering the FOLFOX6m regimen. The trial is expected to run from January 21, 2020, to March 31, 2026, with a maximum treatment period of 6 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histological confirmation of stage II colon adenocarcinoma, and adequate hematological function. Following randomization, participants will receive intravenous administration of **fluorouracil**, **folinic acid**, and **oxaliplatin** as part of the chemotherapy regimen. The study includes regular follow-up visits to monitor treatment response and adverse events, with assessments of DFS, Time to Recurrence (TTR), and Overall Survival (OS) as secondary endpoints. The end-of-study visit will conclude the participant's involvement, with a comprehensive evaluation of treatment outcomes and any long-term effects.
Participant involvement is expected to last up to 6 months, with conditions for early termination including significant adverse reactions, withdrawal of consent, or non-compliance with study protocols. The trial is conducted under strict ethical guidelines, ensuring that all participants provide informed consent prior to any study-specific procedures. The study aims to provide valuable insights into the prognostication and management of stage II colon cancer, potentially influencing future treatment strategies.
Treatment
The clinical trial involves the administration of **Fluorouracil**, marketed as FLUOROURACILE TEVA 1000 mg/20 ml, which is a **solution for injection**. This experimental medication is administered intravenously. The dosage is calculated based on body surface area, with a maximum daily dose of 400 mg/m². The treatment period is set for a maximum of 6 cycles, with each cycle corresponding to a time unit of 3 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial.
**Folinic Acid** is used as a non-experimental treatment in this study. It is provided as a **solution for injection** and is also administered intravenously. The maximum daily dose is 400 mg/m², with a total maximum dose of 4800 mg/m² over the treatment period. Folinic Acid is used in conjunction with chemotherapy to enhance the therapeutic effects of the experimental medication.
Another experimental medication used in the trial is **Oxaliplatin**, marketed as ELOXATINE 5 mg/ml, which is a **solution for infusion**. This medication is administered via intravenous perfusion. The maximum daily dose is 85 mg/m², and the treatment is scheduled for a maximum of 6 cycles, each lasting 3 weeks. The administration of Oxaliplatin is closely monitored to ensure adherence to the dosing regimen.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the improvement of 3-year **Disease Free Survival (DFS)** rates, aiming to increase from 25% to 42.5% with the administration of adjuvant chemotherapy. Secondary endpoints include Time to Recurrence (TTR), Overall Survival (OS), comparison of DFS and OS in circulating tumor DNA (ctDNA) positive versus ctDNA negative patients, toxicities classified using NCI-CTC v4, and the success rate of prognostication of stage II colorectal cancer.
The trial will involve the administration of FOLFOX6m adjuvant treatment to ctDNA positive patients, with efficacy parameters being measured at specified intervals throughout the study. The collection and analysis of these parameters will be conducted using validated clinical methods and tools, ensuring the reliability and accuracy of the data. The trial is designed as a Phase III multicentric, comparative, randomized study, with an estimated end date of March 31, 2026.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed written informed consent obtained prior to any study specific procedures
- Age ≥ 18 years and ≤ 80 years (provided the score of the G8 geriatric questionnaire is >14 for patients 70 years or older)
- Histologically confirmed stage II colon and high rectum adenocarcinoma excluding low and medium rectal cancers (tumor location ≥ 12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery are still eligible), without gross or microscopic evidence of residual disease after surgery with curative intent. Pathology report must be faxed to CRGA just after patient’s randomization.
- At least 12 lymph nodes analyzed
- Patient with MSI + tumors can also be included
- All patients must have been discussed in multidisciplinary meetings with a decision of not performing adjuvant chemotherapy
- No metastatic disease on CT-Scan and/or liver MRI done within 3 months before randomization.
- Randomization planned up to 11 weeks maximun after curative R0 resection
- WHO performance Status < 2
- No prior chemotherapy for colo-rectal cancer
- No prior abdominal or pelvic irradiation for colo-rectal cancer
- Life expectancy of ≥ 5 years
- Adequate haematological function: with neutrophils ≥ 1,500 /mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL (5,6 mmol/l)
- Total bilirubin ≤ 1.5 x ULN (upper limit of normal)
- ASAT and ALAT ≤ 2.5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN
- Serum creatinine ≤ 120 μmol/L or creatinine clearance ≥50 ml/min according MDRD (Modification of Diet in Renal Disease)
- Carcinoembryogenic antigen (CEA) ≤ 1.5 x ULN after surgery (during screening period)
- Negative pregnancy test for registration (for women of childbearing age)
- Patient affiliated to a social security system
Exclusion Criteria
- T4b tumors
- Stage I tumors (T1 or T2N0)
- Peripheral neuropathy > grade 1
- Comorbidity influencing the 5-year patients’ survival including clinically relevant cardiovascular disease
- Ischemic myocardial infarction in the last year and/or unstable ischemic cardiopathy
- Participation to another interventional study for postoperative therapy
- study for postoperative therapy - Partial
- Legal incapacity or physical, psychological social or geographical status interfering with the patient's ability to sign the informed consent or to finish the study
- Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥ 5 years,
- Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women. Men engaging in sexual activity with women of childbearing potential, and women of childbearing potential should agree to use a method of contraception during treatment of the trial and at least 6 months after discontinuation of said treatment.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 21 Jan 2020 | 142 |
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 |
|---|---|---|---|---|---|---|
ELOXATINE 5 mg/ml, solution à diluer pour perfusion | Test | SOLUTION À DILUER POUR PERFUSION | INTRAVENOUS PERFUSION USE | 85 | 6 | PRD482013 |
FLUOROURACILE TEVA 1000 mg/20 ml, solution à diluer pour perfusion | Test | SOLUTION À DILUER POUR PERFUSION | INTRAVENOUS | 400 | 6 | PRD674455 |
FOLINIC ACID | Test | — | INTRAVENOUS | 400 | 6 | SUB13910MIG |