NCT07847229尚未招募2 期
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
Tao Zhang1 个研究点 分布在 1 个国家目标入组 120 人开始时间: 2026年11月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- complete response (CR) rate
研究概览
简要总结
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 ≥10%) and an β-HB-negative stratum (elevation <10%), 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
Arm A
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Short-course radiotherapy (Radiation)
Arm A
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: TME surgery (Procedure)
Arm A
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: PD -1/PD-L1 monoclonal antibody (Drug)
Arm A
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Watch & Wait strategy (Other)
Arm B
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Short-course radiotherapy (Radiation)
Arm B
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: TME surgery (Procedure)
Arm B
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Watch & Wait strategy (Other)
Arm C
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Short-course radiotherapy (Radiation)
Arm C
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: TME surgery (Procedure)
Arm C
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: PD -1/PD-L1 monoclonal antibody (Drug)
Arm C
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Watch & Wait strategy (Other)
Arm D
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Short-course radiotherapy (Radiation)
Arm D
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: TME surgery (Procedure)
Arm D
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Watch & Wait strategy (Other)
Arm D
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Capecitabine (Drug)
Arm A
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Capecitabine (Drug)
Arm A
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Oxaliplatin (Drug)
Arm B
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Oxaliplatin (Drug)
Arm D
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Oxaliplatin (Drug)
Arm B
Experimental
β-HB-Positive (β-HB Elevation ≥10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Capecitabine (Drug)
Arm C
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Oxaliplatin (Drug)
Arm C
Experimental
β-HB-Negative (β-HB Elevation <10%)
- Radiation: Short-course radiotherapy (SCRT): 25 Gy delivered in 5 fractions over 1 week.
- Chemotherapy: 6 cycles of CAPEOX (Capecitabine 1000 mg/m² PO BID D1-14 + Oxaliplatin 130 mg/m² IV D1, q3w) at investigator's discretion.
- PD-1 Inhibitor: Approved anti-PD-1 monoclonal antibody, administered on Day 1 of each chemotherapy cycle for 6 cycles. Dose may be delayed for immune-related adverse events (irAEs) (max delay ≤6 weeks).
- Procedure: Restaging after 6 cycles; TME surgery or Watch & Wait strategy per multidisciplinary evaluation.
干预措施: Capecitabine (Drug)
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
研究点 (1)
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