NCT06417476

Short-course Radiotherapy or Long-course Chemoradiation Followed by mFOLFOXIRI Consolidation Chemotherapy for Organ Preservation in Low Rectal Cancer

A Multicenter, Open, Randomized, Phase II Trial：Short-course Radiotherapy or Long-course Chemoradiation Followed by mFOLFOXIRI Consolidation Chemotherapy for Organ Preservation in Low Rectal Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Sponsor: Pei-Rong Ding · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Given the growing focus on preserving organ function and the utilization of neoadjuvant therapy, it is important to investigate and enhance the application of comprehensive neoadjuvant therapy in low rectal cancer. This approach aims to minimize or circumvent the organ dysfunction and subsequent decline in quality of life associated with radical surgery, with improving disease-free survival (DFS), while . Consequently, we propose to initiate a multicenter clinical trial to examine the medium- and long-term effectiveness of complete neoadjuvant therapy (comprising either short-course radiotherapy or long-course chemoradiation, followed by consolidation chemotherapy with mFOLFOXIRI) in increasing organ preservation rates in patients with low rectal cancer.

Detailed description

This randomised, open-label, multicentre,phase II trial began in December, 2022, as a neoadjuvant trial about short-course radiotherapy or long-course chemoradiation followed by mFOLFOXIRI consolidation chemotherapy,in patients aged 18 years to 70 with clinical stage II-III locally advanced low rectal cancer from six Chinese institutions. The primary endpoint of the study was the 1-year organ preservation rate, with a comparison to historical data. Additionally, the study compared the differences between two radiotherapy regimens within the TNT treatment and explored biomarkers to predict tumor response Patients with local advanced rectal cancer (cT2-4aN0-2,M0, 8cm from the anus verge) were recruited. Patients receive short-course radiotherapy (25Gy/5 times) followed by consolidation chemotherapy or long-course chemoradiation (50Gy/25 times;capecitabine 825 mg/m² twice daily) with mFOLFOXIRI (Irinotecan 150 mg/m2 iv gtt (2h) d1, Oxaliplatin 85 mg/m2 iv gtt (2h) d1, Calcium folinate 400 mg/m2 iv gtt (2h) d1, Total amount of fluorouracil 2400 mg/m2 iv gtt (48h)), treatment repeats every 14 days for 8 courses in the absence of disease progression or unacceptable toxicity. The efficacy evaluation occurs after the fourth and eighth chemotherapy cycle. Patients showing a complete response (CR), partial response (PR), or stable disease (SD) with reduction or stability in tumor size are advised to continue and complete all planned consolidation chemotherapy. However, if the evaluation indicates stable disease with an increase (SD increased) or progressive disease (PD), and if an R0 resection (complete removal of the tumor with no cancer cells at the margins) is feasible, radical total mesorectal excision (TME) should be pursued. In cases where R0 resection is not achievable, the treatment should align with the guidelines for managing unresectable rectal cancer. Upon the final efficacy assessment after the eighth chemotherapy cycle, several pathways are considered based on the outcomes: patients achieving a clinical complete response (cCR) may proceed to a Watch \& Wait approach. Those with a near clinical complete response (near cCR) undergo local transanal resection. If the patient's condition is evaluated as PR/SD with a reduction but does not qualify as near cCR, radical TME is recommended. For patients showing SD with an increase or PD, yet with a potential for R0 resection, radical TME is again the suggested course of action. If R0 resection is unattainable, treatment should adhere to the guidelines for unresectable rectal cancer.

Conditions

• Rectal Neoplasms

Interventions

Type	Name	Description
RADIATION	Short-course radiotherapy	The total dosage was 25Gy consisted of 5 fractions of 5 Gy to clinical target volume without a boost dose
DRUG	Irinotecan	150 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.
DRUG	Oxaliplatin	85 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.
DRUG	Calcium Formate	400 mg/m² iv drip over 2 hours on day 1, repeated every 14 days.
DRUG	Fluorouracil	2400 mg/m² iv drip over 48 hours on day 1-2, repeated every 14 days.
RADIATION	Long-course chemoradiation	The total dosage was 50Gy consisted of 25 fractions of 2 Gy to clinical target volume without a boost dose
DRUG	Capecitabine	825 mg/m² twice daily administered orally and concurrently with radiation therapy for 5 days per week.

Timeline

• Start date: 2022-12-12
• Primary completion: 2025-09-30
• Completion: 2026-12-30
• First posted: 2024-05-16
• Last updated: 2026-04-13

Locations

1 site across 1 country: China