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A Prospective, Biomarker-Stratified Phase 2 Study: β-Hydroxybutyrate as a Predictive Biomarker for Short-Course Radiotherapy Followed by Chemotherapy Plus PD-1 Inhibitor Versus Chemotherapy Alone in Locally Advanced Rectal Cancer
Sponsor: Tao Zhang
Summary
This is a prospective, single-arm, biomarker-stratified, multicenter phase 2 clinical trial. All enrolled patients first receive short-course radiotherapy (SCRT), followed by measurement of serum β-hydroxybutyrate (β-HB) levels to calculate the post-radiotherapy elevation rate. Patients are stratified into an β-HB-positive stratum (elevation significantly) and an β-HB-negative stratum (no elevation), then randomized 1:1 within each stratum to receive either perioperative chemotherapy plus PD-1 inhibitor or perioperative chemotherapy alone. The primary endpoint is the complete response (CR) rate, defined as the composite of pathological complete response (pCR) and clinical complete response (cCR). The study aims to evaluate the efficacy and safety of adding PD-1 inhibitor to perioperative chemotherapy in LARC, and to validate post-radiotherapy β-HB elevation as a predictive biomarker for immunotherapy benefit.
Key Details
Gender
All
Age Range
18 Years - 75 Years
Study Type
INTERVENTIONAL
Enrollment
144
Start Date
2026-11-01
Completion Date
2028-04-30
Last Updated
2026-10-06
Healthy Volunteers
No
Interventions
Short-course radiotherapy
Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.
Capecitabine
1000mg/m2, bid, po, d1-14,q3w
Oxaliplatin
130mg/m2, ivgtt, d1,q3w
TME surgery
The surgery was performed 1 week after the end of neoadjuvant therapy.
PD -1/PD-L1 monoclonal antibody
200 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion.
Watch & Wait strategy
The Watch \& Wait (W\&W) strategy is an organ-preserving clinical management approach for patients with locally advanced rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy. In this strategy, definitive surgical resection (total mesorectal excision, TME) is withheld, and patients are instead managed with a standardized, intensive surveillance regimen to monitor for disease regrowth.
Locations (1)
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China