Actively Recruiting

Phase 2
Age: 18Years - 75Years
All Genders
NCT07448142

Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX for pMMR Locally Advanced Rectal Cancer

Led by Sun Yat-sen University · Updated on 2026-05-07

50

Participants Needed

1

Research Sites

337 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Early response will be assessed after 2 cycles using endoscopy and pelvic MRI to guide subsequent treatment: participants with partial response may discontinue radiotherapy and continue neoadjuvant systemic therapy; participants with stable disease may switch to standard chemoradiotherapy; participants with progressive disease will receive multidisciplinary-team-guided salvage therapy. After 4 cycles, participants with clinical complete response may adopt a watch-and-wait strategy; otherwise, they will undergo radical surgery 2-4 weeks after completion of neoadjuvant therapy. Long-term follow-up will include recurrence and survival outcomes and quality of life.

CONDITIONS

Official Title

Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX for pMMR Locally Advanced Rectal Cancer

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Provided written informed consent before study procedures
  • Aged between 18 and 75 years at enrollment
  • Histologically confirmed rectal adenocarcinoma
  • Tumor located within 10 cm from the anal verge by endoscopy or imaging
  • Locally advanced cancer defined as clinical stage T2N+ or T3-T4a based on pelvic MRI
  • Proficient mismatch repair (pMMR) or microsatellite-stable (MSS) status confirmed by testing
  • No evidence of distant metastasis on chest, abdominal, and pelvic CT scans
  • Circumferential resection margin of 2 mm or more without involvement of mesorectal fascia on baseline MRI
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate organ function including neutrophil count ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, hemoglobin ≥90 g/L
  • Total bilirubin ≤1.5 times upper limit of normal (ULN)
  • AST and ALT ≤2.5 times ULN
  • Creatinine clearance ≥50 mL/min
  • Thyroid-stimulating hormone within normal limits
  • Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during and after the study
  • Men with partners of childbearing potential must agree to use effective contraception during and after the study
Not Eligible

You will not qualify if you...

  • Clinical T4b disease with tumor invading adjacent organs or structures on imaging
  • Circumferential resection margin less than 2 mm or involvement of mesorectal fascia on baseline MRI
  • Evidence of distant metastasis outside the pelvis
  • Prior pelvic or abdominal radiotherapy
  • Prior treatment with immune checkpoint inhibitors or systemic anticancer therapy for rectal cancer
  • Active or past autoimmune disease requiring systemic treatment except low-risk conditions like vitiligo or resolved childhood asthma
  • Use of systemic immunosuppressive therapy above prednisone 10 mg/day within 2 weeks before enrollment
  • Known HIV infection
  • Active hepatitis B or C virus infection requiring treatment
  • Uncontrolled active infection or serious medical condition compromising safety or compliance
  • History of another malignancy within 5 years except certain low-risk skin or cervical cancers
  • Known allergy or hypersensitivity to pucotenlimab, oxaliplatin, capecitabine, or their components
  • Pregnant or breastfeeding women
  • Any condition making participation unsuitable as judged by the investigator

AI-Screening

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Trial Site Locations

Total: 1 location

1

Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651

Guangzhou, Guanggong, China, 510060

Actively Recruiting

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Research Team

W

Wu Jiang

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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