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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- complete response (CR) rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients or their family members agree to participate in the study and sign the informed consent form;
- •Age 18-75 years, male or female;
- •Histologically confirmed Locally Advanced rectal adenocarcinoma;
- •inferior margin ≤ 10 cm from the anal verge;
- •ECOG performance status score is 0-1;
- •Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc;
- •There was no operative contraindication;
- •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;
- •Urinary protein < 2+ or 24-hour urinary protein excretion < 1 g at baseline.
排除标准
- •Patients with non-pMMR LARC；
- •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;
- •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).
研究组 & 干预措施
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 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.
干预措施: Short-course radiotherapy (Radiation)
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 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.
干预措施: Capecitabine (Drug)
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 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.
干预措施: Oxaliplatin (Drug)
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 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.
干预措施: TME surgery (Procedure)
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 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.
干预措施: β-hydroxybutyrate (Dietary Supplement)
结局指标
主要结局
complete response (CR) rate
时间窗: an expected average of 12 months
Defined as pathological complete response (pCR) + Clinical complete response (cCR)
次要结局
- 3-year disease-Free Survival(an expected average of 3 years)
- Overall Survival(an expected average of 5 years)
- Adverse events (AEs) were graded according to the NCI CTCAE version 5·0(an expected average of 1.5 years)
研究者
Tao Zhang
MD
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology