β-hydroxybutyrate with short-course radiotherapy, immunotherapy and CAPEOX before surgery for 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 phase II trial will test whether adding β-hydroxybutyrate supplements to short-course radiotherapy followed by immunotherapy plus CAPEOX chemotherapy improves outcomes for people with locally advanced rectal cancer before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07239466 on ClinicalTrials.gov

What this trial studies

This prospective phase II trial will enroll adults with histologically confirmed locally advanced rectal adenocarcinoma (inferior margin ≤10 cm from the anal verge) and ECOG performance status 0–1. Participants will receive short-course radiotherapy with concurrent β-hydroxybutyrate supplementation, followed by sequential immunotherapy combined with CAPEOX (capecitabine and oxaliplatin) as neoadjuvant treatment prior to total mesorectal excision (TME). Laboratory monitoring and predefined safety criteria are required, and treatment response and surgical outcomes will be recorded. The study is single-center at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China.

Who should consider this trial

Good fit: Adults aged 18–75 with untreated, histologically confirmed locally advanced rectal adenocarcinoma within 10 cm of the anal verge, ECOG 0–1, adequate blood counts and organ function, and who can give informed consent are ideal candidates.

Not a fit: Patients with prior rectal cancer treatment, metastatic disease, significant organ dysfunction, poor performance status, or who cannot attend the Wuhan treatment site are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase preoperative tumor response and possibly raise the rate of complete pathological responses or organ-preserving outcomes.

How similar studies have performed: Neoadjuvant CAPEOX with radiotherapy and emerging immunotherapy approaches have shown promise in rectal cancer, but adding β-hydroxybutyrate supplementation is novel and has limited clinical data to date.

Eligibility criteria

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).

Where this trial is running

Wuhan, Hubei

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Principal investigator: Zhenyu Lin — Huazhong University of Science and Technology Tongji Medical College Union Hospital
• Study coordinator: Zhenyu Lin, MD

Conditions Rectal Cancer; Radiotherapy; Immunotherapy; Chemotherapy