NCT06899477

Pre-Operative Treatment in REseCTable COlon CanceR

Pre-Operative Treatment in REseCTable COlon CanceR (PROTECTOR/FIRE-10; AIO-KRK-0620; IAG-VO-0323) Prospective, Randomized, Open, Multicenter Phase III Trial to Investigate the Efficacy Preoperative Systemic Therapy in Advanced Colon Cancer

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 714 (estimated)
• Sponsor: Dominik Paul Modest · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, randomized, controlled, multicenter, phase III study with two parallel arms. Patients with advanced colon cancer, including the upper third of the rectum, clinically staged cT3-4 and or cN+ (defined as lymph nodes with short axis of at least 1cm) are randomized in a 2:1 fashion (favoring preoperative therapy= Arm A) to investigate the efficacy, patient reported quality of life and safety of preoperative mFOLFOXIRI or mFOLFOX-6 or CAPOX followed by surgery versus the standard of care algorithm (surgery followed by stage-guided adjuvant therapy as recommended by the local multidisciplinary tumor board (Arm B)).

Detailed description

The trial will consist of a clinical and translational part. After completion of the treatment algorithm in both arms of the trial, follow-up as scheduled by current guidelines is recommended. Additionally, assessment of quality of life and blood sampling (tumor markers, circulating tumor DNA and potential innovative markers) will be performed for up to 5 years on a three-months basis. During the active part of the study, a radiologic re-assessment prior to surgery will be recommended for all trial subjects of arm A. Tumor biopsies and resected tumor specimens will be collected at screening (baseline sample) and in the course of treatment. Additionally, in case of disease relapse a tumor re-biopsy will be collected as far as considered feasible and safe for the patient by the investigator. The objective of the re-assessments is detection of relapse either radiologically or within the translational material (blood samples with ctDNA dynamics and tumor - if available from relapses). Patients in Arm A will receive a preoperative study drug intervention (mFOLFOXIRI or mFOLFOX-6 or CAPOX) for up to 3 months (6 cycles biweekly or 4 cycles triweekly) after randomization with clinical and safety assessments as specified in (Table 1). Allocation to study treatment FOLFOX/FOLFOXIRI or CAPOX for patients in Arm A is stratified and done by investigator's choice. Beyond clinical or radiological factors, the decision may consider but is not limited to factors such as age, performance status, and patients' perspectives. Since obligatory criteria cannot be made, treatment allocation will not be regulated by the protocol, but stratification will avoid that treatment allocation promotes bias.

Conditions

• Colo-rectal Cancer
• Colon Cancer
• Colon Carcinoma

Interventions

Type	Name	Description
DRUG	mFOLFOXIRI	Up to 6 cycles, every 2 weeks, mFOLFOXIRI: Oxaliplatin 85 mg/m2 2 h day 1, Irinotecan 150 mg/m2 60-90 min day 1, Folinic acid 400 mg/m2 \~1 h day 1, followed by 5-FU 2400 mg/m2 46 h
DRUG	mFOLFOX-6	Up to 6 cycles, every 2 weeks, mFOLFOX-6: Oxaliplatin 85 mg/m2 2 h day 1, Folinic acid 400 mg/m2 \~1 h day 1, (optional: 5-FU 400 mg/m2 bolus), followed by 5-FU 2400 mg/m2 46 h.
DRUG	CAPOX	Up to 4 cycles, every 3 weeks, CAPOX: Oxaliplatin 130 mg/m2 3 h day 1, Capecitabine 1000 mg/m2 ORALLY taken twice daily d1-d14

Timeline

• Start date: 2025-04-01
• Primary completion: 2033-04-01
• Completion: 2035-04-01
• First posted: 2025-03-28
• Last updated: 2025-03-28

Locations

28 sites across 1 country: Germany