Phase III Randomized Trial of Neoadjuvant CAPOX or FOLFOX Chemotherapy in Obstructive Colon Cancer Post-Colostomy for Curative Therapeutic Sequence Evaluation
- Trial ID
- 2024-516456-17-00
- Protocol
- 2019/0407/HP
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine whether **CAPOX** or **FOLFOX** neoadjuvant chemotherapy, as part of a perioperative strategy in patients with obstructive colon cancer (OCC) who have undergone colostomy to relieve obstruction, can improve the rate of complete curative therapeutic sequence compared to an adjuvant chemotherapy strategy. This is clinically relevant as it may enhance treatment outcomes and potentially improve survival rates in patients with OCC.
Secondary objectives include evaluating:
- Tolerability (grade 3, 4, and 5 toxicity) and compliance (number of cycles) of neoadjuvant chemotherapy.
- Tolerability (grade 3, 4, and 5 toxicity) of adjuvant chemotherapy.
- Primary tumour resection, focusing on the rate, quality, and completeness of surgical excision.
- Postoperative morbidity according to the Dindo classification.
- Disease-free survival at 3 years.
- Overall survival at 3 years.
- Survival without stoma at 3 years.
- Quality of life at specified intervals during and after treatment.
Participants
The clinical trial involves participants diagnosed with **obstructive colon cancer** who have undergone a defunctioning stoma procedure. The study population includes both male and female subjects aged 18 years and older. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial excludes individuals with a history of colorectal cancer, serious medical co-morbidities, or prior chemotherapy or abdominal or pelvic irradiation. Participants must have pathologically confirmed adenocarcinoma, non-metastatic status on thoracic-abdomino-pelvis CT scan, and meet specific laboratory criteria. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **neoadjuvant chemotherapy** in patients with obstructive colon cancer who have undergone colostomy. This is a randomized, phase III trial comparing two chemotherapy regimens: CAPOX and FOLFOX. The trial aims to determine if these regimens, when used in a perioperative strategy, can improve the rate of complete curative therapeutic sequence compared to an adjuvant chemotherapy strategy. The study is double-blind and controlled, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias.
The trial is expected to commence recruitment on May 7, 2024, and is estimated to conclude by October 7, 2031. Participants will be involved in the study for a maximum treatment period of six months, depending on the assigned regimen. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and side effects, and an end-of-study visit to assess the overall outcome and gather final data. The inclusion criteria require participants to be adults aged 18 years or older, with a confirmed diagnosis of obstructive colon cancer, and no prior history of colorectal cancer or serious medical comorbidities that could compromise their ability to tolerate chemotherapy or surgery.
Participants may be withdrawn from the study early if they experience unacceptable toxicity, fail to comply with the study protocol, or if the investigator deems it in the participant's best interest. The primary endpoint of the trial is the success of a full curative therapeutic sequence, with secondary endpoints focusing on safety and tolerability. The trial will utilize **fluorouracil**, **capecitabine**, **oxaliplatin**, and **levoleucovorin** as part of the chemotherapy regimens, administered via injection or orally, depending on the specific treatment protocol. The study is not classified as low intervention, reflecting the complexity and potential risks associated with the treatment regimens being tested.
Treatment
The clinical trial involves the administration of several **experimental medications**. The first medication is **FLUOROURACIL**, marketed as FLUOROURACILE ACCORD 50 mg/ml, which is a **solution for infusion**. This medication is administered via **injection**. The maximum daily dose is 1200 mg, with a total maximum dose of 2400 mg over a treatment period of up to 6 months. The pharmaceutical form is a solution to be diluted for infusion, and it is produced by Accord Healthcare France SAS.
The second medication is **CAPECITABINE**, marketed as Xeloda 150 mg film-coated tablets. This medication is administered **orally**. The maximum daily dose is 2000 mg, with a total maximum dose of 2000 mg over a treatment period of up to 3 months. The pharmaceutical form is a film-coated tablet, and it is produced by Cheplapharm Arzneimittel GmbH.
The third medication is **OXALIPLATIN**, marketed as ELOXATINE 5 mg/ml, which is also a **solution for infusion**. This medication is administered via **injection**. The maximum daily dose is 130 mg, with a total maximum dose of 130 mg over a treatment period of up to 6 months. The pharmaceutical form is a solution to be diluted for infusion, and it is produced by Sanofi Winthrop Industrie.
The fourth medication is **LEVOLEUCOVORIN**, marketed as ELVORINE 100 mg/10 mL, which is a **solution for injection**. This medication is administered via **injection**. The maximum daily dose is 400 mg, with a total maximum dose of 400 mg over a treatment period of up to 6 months. The pharmaceutical form is a solution for injection, and it is produced by Pfizer Holding France.
All medications are of chemical origin and are used in the context of a randomized phase III trial to evaluate the efficacy of neoadjuvant chemotherapy in patients with obstructive colon cancer. The trial aims to compare the effectiveness of CAPOX and FOLFOX regimens in improving the rate of complete curative therapeutic sequences compared to an adjuvant chemotherapy strategy. Participant compliance with the dosing schedule is monitored throughout the trial period.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the success of a full curative therapeutic sequence in patients with obstructive colon cancer. The trial aims to determine whether neoadjuvant chemotherapy with CAPOX or FOLFOX, in a perioperative strategy, improves this outcome compared to an adjuvant chemotherapy strategy. The assessment will focus on the rate of complete curative therapeutic sequences achieved.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 years
- ECOG performance status 0 or 1
- Patients with obstructive colon cancer treated by defunctioning stoma
- Pathologically confirmed adenocarcinoma (≥10 cm from the anal verge) MSS/pMMR (microsatellite stable primary tumor) status
- Patient requiring colectomy
- Laboratory data including : White blood cell count ≥ 3.109 /L with Neutrophils ≥ 1,5.109 / L, Platelet count ≥ 100.109 / L, 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 ≤ 1,5 x ULN, Serum creatinine ≤ 1,5 x ULN (performed 10-15 days prior to randomization)
- Non metastatic colon cancer on thoracic-abdomino-pelvis CT scan
- no suspicion of 2nd colon cancer
- No prior chemotherapy or abdominal or pelvic irradiation
- No history of colorectal cancer
- No serious medical co-morbidity (uncontrolled inflammatory bowel disease, uncontrolled angina, recent [within the past 6 months] myocardial infarction, or another serious medical condition) judged to compromise ability to tolerate chemotherapy and/or surgery
- women participating in the study, contraception is required during chemotherapy treatment and for 15 months after cessation of chemotherapy treatment a) For Women of childbearing potential an effective contraception is required and a negative blood pregnancy test by beta-HCG at inclusion and monthly pregnancy tests throughout the study until the end of systemic treatment exposure b) For women surgically sterile the absence of ovaries and/or uterus is confirmed. c) For postmenauposal women a confirmation diagnostic (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit) is required
- For men participating in the study, contraception is required during the trial and for 12 months after stopping chemotherapy treatment
- Patient able to comply with the study protocol, in the investigator’s judgment
- Patient affiliated with, or beneficiary of a social security (health insurance) category
- Person informed and having signed his consent
Exclusion Criteria
- Contraindication to colectomy and/or anesthesia 2. Rectal cancer located within 10 cm of the anal verge by endoscopy or under the peritoneal reflection at surgery or having received radiation therapy prior to surgery 3. Patient having received radiation therapy prior to surgery 4. Metastatic spread at baseline assessment (lung, liver, peritoneal) 5. History or current evidence on physical examination of central nervous system disease or; Peripheral neuropathy ≥ grade 1 common toxicity criteria for adverse events NCI-CTCAE (version 5.0) 6. Contraindication to study chemotherapy treatments 7. Presence of inflammatory bowel disease HNPCC syndrome or polyposis 8. Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia 9. Uracilemia ≥ 150 ng/ml (suggestive of complete DPD deficiency) 10. Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent 11. Any significant disease, which, in the investigator’s opinion, would exclude the patient from the study. 12. Patient is a pregnant (positive blood pregnancy test) or breastfeeding (lactating) woman or intending to become pregnant during the study and for at least 15 months after the chemotherapy treatment termination 13. Person deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision) 14. Simultaneous participation in another interventional research
- Rectal cancer located within 10 cm of the anal verge by endoscopy or under the peritoneal reflection at surgery or having received radiation therapy prior to surgery
- Patient having received radiation therapy prior to surgery
- Metastatic spread at baseline assessment (lung, liver, peritoneal)
- History or current evidence on physical examination of central nervous system disease or; Peripheral neuropathy ≥ grade 1 common toxicity criteria for adverse events NCI-CTCAE (version 5.0)
- Contraindication to study chemotherapy treatments
- Presence of inflammatory bowel disease HNPCC syndrome or polyposis
- Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
- Uracilemia ≥ 150 ng/ml (suggestive of complete DPD deficiency)
- Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent
- Any significant disease, which, in the investigator’s opinion, would exclude the patient from the study.
- Patient is a pregnant (positive blood pregnancy test) or breastfeeding (lactating) woman or intending to become pregnant during the study and for at least 15 months after the chemotherapy treatment termination
- Person deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision)
- Simultaneous participation in another interventional research
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 07 May 2024 | 232 |
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 |
|---|---|---|---|---|---|---|
ELVORINE 100 mg/10 mL, solution injectable | Test | SOLUTION INJECTABLE | INJECTION | 400 | 6 | PRD422519 |
ELOXATINE 5 mg/ml, solution à diluer pour perfusion | Test | SOLUTION À DILUER POUR PERFUSION | INJECTION | 130 | 6 | PRD482013 |
FLUOROURACILE ACCORD 50 mg/ml, solution à diluer pour perfusion | Test | SOLUTION À DILUER POUR PERFUSION | INJECTION | 1200 | 6 | PRD415414 |
OXALIPLATIN | Test | — | INJECTION | 85 | 6 | SUB09490MIG |
Xeloda 150 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 2000 | 3 | PRD9863933 |