Neoadjuvant Moderately Hypofractionated Radiotherapy Combined With Chemotherapy and Immunotherapy for High-risk pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Multi-center Randomized Control Phase II Trial

NCT07527520 | Not Yet Recruiting Phase 2

• 1 other identifier: KY2026078
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to observe and evaluate the efficacy and safety of moderately hypofractionated radiotherapy combined with chemotherapy and immunotherapy, compared with conventional neoadjuvant chemoradiotherapy, in patients with high-risk locally advanced colorectal cancer.

Conditions

Rectal Cancer; Moderately Hypofractionated Radiotherapy; Serplulimab; pMMR/MSS

Outcome Measures

Primary Outcomes (1)

• Complete Remission (CR) Rate

  Definition: The proportion of participants achieving complete remission, defined as: Pathologic complete response (pCR): No residual viable tumor cells detected in the resected specimen after neoadjuvant treatment (ypT0N0) Sustained clinical complete response (cCR): No evidence of residual tumor on digital rectal examination, endoscopy, and MRI, maintained for more than 1 year without surgery Assessment Method: Evaluated by investigators based on imaging, endoscopic findings, pathology (for surgical cases), and clinical examination

  At the time of surgery for pCR, and at 1 year after achieving cCR for sustained cCR

Secondary Outcomes (5)

• 3-Year Disease-Free Survival (DFS) Rate

  Up to 3 years after randomization

• 3-Year Overall Survival (OS) Rate

  up to 5 years

• 3-Year Event-Free Survival (EFS) Rate

  up to 3 years from treatment

• Objective Response Rate

  Up to 1 years

• AE rate

  24months

Other Outcomes (1)

• Quality of life (QoL)

  From date of randomization until the date of death from any cause, assessed up to 10 years

Study Arms (3)

Experimental group A

EXPERIMENTAL

CapOx+Serplulimab+Moderately Hypofractionated Radiotherapy

Drug: Serplulimab

Experimental group B

EXPERIMENTAL

CapOx+Serplulimab+Long-course radiotherapy

Radiation: Moderately Hypofractionated Radiotherapy

Control arm

ACTIVE COMPARATOR

CapOx+Long-course radiotherapy

Other: CapOx+Long-course radiotherapy

Interventions

Moderately Hypofractionated Radiotherapy RADIATION

CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle. Serplulimab: 300 mg intravenously on day 1 of each 21-day cycle. Moderately Hypofractionated Radiotherapy：Delivered using a simultaneous integrated boost (SIB) technique.Gross tumor volume (GTV): 3.5 Gy per fraction; clinical target volume (CTV): 3.0 Gy per fraction.Once daily, 5 fractions per week, for a total of 10 fractions.Total dose: GTV 35 Gy, CTV 30 Gy.

Experimental group B

Serplulimab DRUG

CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle. Serplulimab: 300 mg intravenously on day 1 of each 21-day cycle. Long-course Concurrent Chemoradiotherapy：Delivered using a conventional fractionation schedule.Gross tumor volume (GTV): 1.8-2.0 Gy per fraction, total dose 50-50.4 Gy.Clinical target volume (CTV): 1.8 Gy per fraction, total dose 45 Gy.Once daily, 5 fractions per week.GTV receives 25-28 fractions; CTV receives 25 fractions.

Experimental group A

CapOx+Long-course radiotherapy OTHER

CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle. Long-course Concurrent Chemoradiotherapy：Delivered using a conventional fractionation schedule.Gross tumor volume (GTV): 1.8-2.0 Gy per fraction, total dose 50-50.4 Gy.Clinical target volume (CTV): 1.8 Gy per fraction, total dose 45 Gy.Once daily, 5 fractions per week.GTV receives 25-28 fractions; CTV receives 25 fractions.

Control arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 75 years.
• Histologically confirmed colorectal adenocarcinoma with the lower margin of the lesion ≤ 10 cm from the anal verge as assessed by MRI, and immunohistochemistry confirming pMMR, or genetic testing demonstrating MSI-L or MSS.
• Presence of at least one of the following high-risk factors as assessed by pelvic MRI: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph node (longest diameter \> 7 mm).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
• No prior surgery, radiotherapy, chemotherapy, or targeted therapy.
• Able to tolerate radiotherapy, chemotherapy, and immunotherapy: ECOG performance status score 0-2. Laboratory results: white blood cell count ≥ 4.0 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 80 g/L, ALT \< 2 × ULN, total bilirubin \< 35 μmol/L, serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 50 mL/min, thyroid-stimulating hormone within normal range (patients with stable thyroid function after hormone replacement therapy may be enrolled).
• Willing to participate and able to provide written informed consent.

You may not qualify if:

• Presence of distant metastasis.
• Patients with stage I or II rectal cancer who do not require preoperative neoadjuvant therapy.
• Severe diseases involving the heart, lung, brain, kidney, gastrointestinal tract, or other systemic conditions.
• Untreated chronic hepatitis B or HBV carriers with HBV DNA \> 500 IU/mL, or patients positive for HCV RNA. Patients with inactive hepatitis B surface antigen (HBsAg) carriers, those with hepatitis B who have been treated and are stable (HBV DNA \< 500 IU/mL), and those who have been cured of hepatitis C may be enrolled.
• Active autoimmune disease or history of autoimmune disease with potential for relapse.
• Receipt of corticosteroids (at a dose equivalent to prednisone \> 10 mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration.
• History of thyroid dysfunction.
• Severe chronic or active infection requiring systemic antifungal or antiviral therapy, including tuberculosis infection.
• History of allergic constitution or allergy to multiple drugs.
• History of prior pelvic radiotherapy.
• History of inflammatory bowel disease.
• Unwillingness to participate or inability to provide written informed consent.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Zhongshan hosptial, Fudan University

Shanghai, 200032, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)