NCT07040098

Optimizing Immunotherapy Combined With Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

A Prospective, Multicenter, Randomized Clinical Trial of Optimizing Immunotherapy Combined With Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer (STELLARIII)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 228 (estimated)
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study explores the key clinical issues in the field of neoadjuvant therapy for locally advanced rectal cancer. There are three core problems with the currently recommended total neoadjuvant therapy (TNT) in the guidelines: the lack of evidence-based consensus on the timing of radiotherapy and chemotherapy, the undefined number of chemotherapy cycles, and the uncertainty in the selection of the precise radiotherapy mode. In recent years, the combination of immune checkpoint inhibitors (ICIs) with the PD-1/PD-L1 inhibitors as the core and the TNT regimen has shown a trend of further enhancing tumor regression, providing a possibility for the organ function preservation of rectal cancer. However, existing clinical studies exhibit a high degree of heterogeneity in treatment strategies. In particular, there is a lack of high-quality evidence-based medical evidence in core aspects such as the timing of ICIs intervention and the combination of treatment regimens. This study is designed as a prospective, multicenter, randomized controlled phase II study. The "pick the winner" strategy for screening the optimal regimen is adopted to evaluate the efficacy of four neoadjuvant regimens (Group SCRT-4: short-course radiotherapy → 4 cycles of chemotherapy + ICIs; Group SCRT-6: short-course radiotherapy → 6 cycles of chemotherapy + ICIs; Group LCRT-4: concurrent chemoradiotherapy → 4 cycles of chemotherapy + ICIs; Group LCRT-6: concurrent chemoradiotherapy → 6 cycles of chemotherapy + ICIs). By evaluating indicators such as the complete response rate, organ preservation rate, safety, long-term survival, as well as the anal function and quality of life of patients, treatment strategies with clinical advantages will be screened out, providing an evidence-based basis for subsequent phase III confirmatory trials.

Conditions

• Locally Advanced Rectal Cancer (LARC)

Interventions

Type	Name	Description
DRUG	Sintilimab	PD-1 inhibitor
RADIATION	Short-course radiotherapy	Pelvic radiation, SCRT, 5 Gy x 5 alone
RADIATION	Long-course concurrent chemoradiotherapy	Pelvic radiation, 50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine (825 mg/m2, twice a day).
COMBINATION_PRODUCT	CAPOX	chemotherapy regimen, Oxaliplatin 130 mg/m2 IV day 1，Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle)

Timeline

• Start date: 2025-06-01
• Primary completion: 2027-06-30
• Completion: 2030-06-30
• First posted: 2025-06-26
• Last updated: 2025-06-26

Locations

2 sites across 1 country: China