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

Tao Zhang

Status and phase: Not yet enrolling; Phase 2

Conditions: Chemotherapy; Immunotherapy; Radiotherapy; Rectal Cancer

Treatments: Radiation: Short-course radiotherapy; Procedure: TME surgery; Drug: Capecitabine; Drug: Oxaliplatin; Dietary Supplement: β-hydroxybutyrate

Study type: Interventional

Funder types: Other

Identifiers

NCT07239466

Union-BHB

Details and patient eligibility

About

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.

Enrollment: 48 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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48 participants in 1 patient group

experimental group

Experimental group

Description:

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 2 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 2 cycles during the neoadjuvant phase.

Treatment:

Dietary Supplement: β-hydroxybutyrate

Drug: Oxaliplatin

Drug: Capecitabine

Procedure: TME surgery

Radiation: Short-course radiotherapy