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Not yet recruitingNCT07847229Updated Sep 29, 2026

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

A Phase 2 interventional study of Short-course radiotherapy and Capecitabine in Rectal Cancer, Radiotherapy and Immunotherapy, sponsored by Tao Zhang. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Tao Zhang · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Rectal Cancer
  • Radiotherapy
  • Immunotherapy
  • Chemotherapy

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03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Arm A

    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.

    Radiation: Short-course radiotherapy · Drug: Capecitabine · Drug: Oxaliplatin · Procedure: TME surgery · Drug: PD -1/PD-L1 monoclonal antibody · Other: Watch & Wait strategy

  • Experimental
    Arm B

    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.

    Radiation: Short-course radiotherapy · Drug: Capecitabine · Drug: Oxaliplatin · Procedure: TME surgery · Other: Watch & Wait strategy

  • Experimental
    Arm C

    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.

    Radiation: Short-course radiotherapy · Drug: Capecitabine · Drug: Oxaliplatin · Procedure: TME surgery · Drug: PD -1/PD-L1 monoclonal antibody · Other: Watch & Wait strategy

  • Experimental
    Arm D

    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.

    Radiation: Short-course radiotherapy · Drug: Capecitabine · Drug: Oxaliplatin · Procedure: TME surgery · Other: Watch & Wait strategy

Interventions

  • RadiationShort-course radiotherapy

    Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.

  • DrugCapecitabine

    1000mg/m2, bid, po, d1-14,q3w

  • DrugOxaliplatin

    130mg/m2, ivgtt, d1,q3w

  • ProcedureTME surgery

    The surgery was performed 1 week after the end of neoadjuvant therapy.

  • DrugPD -1/PD-L1 monoclonal antibody

    200 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion.

  • OtherWatch & Wait strategy

    The Watch \& Wait (W\&W) strategy is an organ-preserving clinical management approach for patients with locally advanced rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy. In this strategy, definitive surgical resection (total mesorectal excision, TME) is withheld, and patients are instead managed with a standardized, intensive surveillance regimen to monitor for disease regrowth.

05

What researchers measure

Primary outcomes

  1. complete response (CR) rate

    Defined as pathological complete response (pCR) + Clinical complete response (cCR)

    Time frame: an expected average of 12 months

Secondary outcomes

  1. 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

    Time frame: an expected average of 3 years

  2. Overall Survival

    The time from the date of randomization to the death caused by any cause

    Time frame: an expected average of 5 years

  3. Adverse events (AEs) were graded according to the NCI CTCAE version 5·0

    Adverse events and surgical safety

    Time frame: an expected average of 1.5 years

06

Study locations

1 site
  • Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
    Wuhan, Hubei 430000, China
07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07847229
Lead sponsor
Tao Zhang
Responsible party
Tao Zhang (MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) — Sponsor-investigator
First posted
Sep 29, 2026
Start date
Nov 1, 2026 (estimated)
Primary completion
Oct 31, 2027 (estimated)
Completion
Apr 30, 2028 (estimated)
Last update
Sep 29, 2026

Study contacts

Zhenyu Lin
Contact
whxhlzy@hust.edu.cn
15827130393
Tao Zhang
Contact
taozhangxh@hust.edu.cn
Zhenyu Lin
principal investigator · Huazhong University of Science and Technology Tongji Medical College Union Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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