NCT07847229

Brief 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.

Trial Health

63
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for phase_2

Timeline
18mo left

Started Nov 2026

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 23, 2026

Completed
6 days until next milestone

First Posted

Study publicly available on registry

September 29, 2026

Completed
1 month until next milestone

Study Start

First participant enrolled

November 1, 2026

Expected
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2027

6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2028

Last Updated

September 29, 2026

Status Verified

September 1, 2026

Enrollment Period

12 months

First QC Date

September 23, 2026

Last Update Submit

September 23, 2026

Conditions

Rectal CancerRadiotherapyImmunotherapyChemotherapy

Outcome Measures

Primary Outcomes (1)

  • complete response (CR) rate

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

    an expected average of 12 months

Secondary Outcomes (3)

  • 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

Study Arms (4)

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.

Radiation: Short-course radiotherapyDrug: CapecitabineDrug: OxaliplatinProcedure: TME surgeryDrug: PD -1/PD-L1 monoclonal antibodyOther: Watch & Wait strategy

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.

Radiation: Short-course radiotherapyDrug: CapecitabineDrug: OxaliplatinProcedure: TME surgeryOther: Watch & Wait strategy

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.

Radiation: Short-course radiotherapyDrug: CapecitabineDrug: OxaliplatinProcedure: TME surgeryDrug: PD -1/PD-L1 monoclonal antibodyOther: Watch & Wait strategy

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.

Radiation: Short-course radiotherapyDrug: CapecitabineDrug: OxaliplatinProcedure: TME surgeryOther: Watch & Wait strategy

Interventions

Short-course radiotherapyRADIATION

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

Arm AArm BArm CArm D
CapecitabineDRUG

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

Arm AArm BArm CArm D
OxaliplatinDRUG

130mg/m2, ivgtt, d1,q3w

Arm AArm BArm CArm D
TME surgeryPROCEDURE

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

Arm AArm BArm CArm D
PD -1/PD-L1 monoclonal antibodyDRUG

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

Arm AArm C
Watch & Wait strategyOTHER

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.

Arm AArm BArm CArm D

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

CapecitabineOxaliplatin

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesCoordination ComplexesOrganic Chemicals

Study Officials

  • Zhenyu Lin

    Huazhong University of Science and Technology Tongji Medical College Union Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Lin

CONTACT

15827130393whxhlzy@hust.edu.cn

Tao Zhang

CONTACT

taozhangxh@hust.edu.cn

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

September 23, 2026

First Posted

September 29, 2026

Study Start (Estimated)

November 1, 2026

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

April 30, 2028

Last Updated

September 29, 2026

Record last verified: 2026-09

Locations

CN(1)