A Pilot Study Evaluating β-hydroxybutyrate Supplementation Concomitant to Short-Course Radiotherapy Followed by Immunotherapy Combined With CAPEOX Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer

A Single-Arm, Single-Center Study of Exploring the β-hydroxybutyrate Supplementation and Short-Course Radiotherapy Followed by Immunotherapy Combined With CAPEOX Neoadjuvant Therapy in Locally Advanced Rectal Cancer

This study is a prospective phase II clinical trial aimed at exploring the potential benefits of supplementing β-hydroxybutyrate with existing short course radiotherapy sequential immunotherapy and CAPEOX therapy.

Study Overview

• Status: Recruiting
• Conditions: Chemotherapy; Rectal Cancer; Radiotherapy; Immunotherapy
• Intervention / Treatment: Procedure: TME surgery; Radiation: Short-course radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Dietary supplement: β-hydroxybutyrate

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenyu Lin, MD; Phone Number: 027-83262683; Email: whxhlzy@hust.edu.cn
• Study Contact Backup: Name: Tao Zhang, MD; Email: whxhlzy@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Tao Zhang, MD; Phone Number: 027-83262683; Email: 1277577866@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients or their family members agree to participate in the study and sign the informed consent form;
2. Age 18-75 years, male or female;
3. Histologically confirmed Locally Advanced rectal adenocarcinoma;
4. inferior margin ≤ 10 cm from the anal verge;
5. ECOG performance status score is 0-1;
6. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc;
7. There was no operative contraindication;
8. Laboratory tests were required to meet the following requirements: white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
9. Urinary protein < 2+ or 24-hour urinary protein excretion < 1 g at baseline.

Exclusion Criteria:

1. Patients with non-pMMR LARC；
2. Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms;
3. Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: experimental group; Radiotherapy (SCRT): Total dose 25 Gy delivered in 5 fractions (5 Gy per fraction, once daily over 5 consecutive days). β-hydroxybutyrate: Oral β-hydroxybutyrate supplement (5g/day, starting from the day of first radiotherapy, lasting for 2 weeks). Immunotherapy (PD-1 monoclonal antibody): 200 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion. Chemotherapy (CAPEOX regimen): Oxaliplatin: 130 mg/m² IV infusion over 120 minutes on Day 1. Capecitabine: 1000 mg/m² orally twice daily (morning and evening, 30 minutes after meals) on Days 1-14. Cycle duration: 3 weeks per cycle; total of 6 cycles during the neoadjuvant phase.

Procedure: TME surgery; The surgery was performed 1 week after the end of neoadjuvant therapy.; Radiation: Short-course radiotherapy; Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.; Drug: Capecitabine; 1000mg/m2, bid, po, d1-14,q3w; Drug: Oxaliplatin; 130mg/m2, ivgtt, d1,q3w; Dietary supplement: β-hydroxybutyrate; Oral β-hydroxybutyrate supplement (5g/day, starting from the day of first radiotherapy, lasting for 2 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response (CR) rate	Defined as pathological complete response (pCR) + Clinical complete response (cCR)	an expected average of 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time from the date of randomization to the death caused by any cause	an expected average of 5 years
3-year disease-Free Survival	The time from the first day of disease free (operation date) to local or distant recurrence, or the death event caused by any reason, whichever occurs first	an expected average of 3 years
Adverse events (AEs) were graded according to the NCI CTCAE version 5·0	Adverse events and surgical safety	an expected average of 1.5 years

Collaborators and Investigators

• Sponsor: Tao Zhang
• Investigators: Principal Investigator: Zhenyu Lin, Huazhong University of Science and Technology Tongji Medical College Union Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 15, 2025
• First Submitted That Met QC Criteria: November 15, 2025
• First Posted (Actual): November 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin
• Other Study ID Numbers: Union-BHB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No