Phase II RCT of LCRT vs SCRT + CAPOX/PD-1i/COX-2i in MSS Locally Advanced Rectal Cancer

NCT07154316 | Recruiting Phase 2

• 1 other identifier: SERRAC
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 5

Brief Summary

This randomized phase II trial evaluates the efficacy of long-course chemoradiotherapy (50Gy/25Fx + capecitabine) versus short-course radiotherapy (25Gy/5Fx) combined with CAPOX（Capecitabine and Oxaliplatin）, PD-1 inhibitor (serplulimab), and COX-2 inhibitor (celecoxib) in MSS（MicroSatellite Stable） locally advanced rectal cancer, with primary endpoint of complete response rate (pCR+cCR)（Complete Remission） and secondary endpoints including anal preservation rate and 3-year survival outcomes, aiming to elucidate the immunomodulatory effects of triple therapy on tumor microenvironment.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• CR (Complete Response)

  Complete response (CR) in malignant tumor patients is defined as the complete disappearance of all target lesions, normalization of tumor marker levels, and absence of new lesions for ≥4 weeks after treatment.

  3 years

Secondary Outcomes (6)

• sphincter preservation rate

  3 years

• Grade 3 or higher toxicity rate

  3 years

• 3yPFS (Progression-Free Survival)

  3 years

• 3yLRFS (Local Recurrence-Free Survival)

  3 years

• 3yOS (Overall Survival)

  3 years

Study Arms (2)

Long-course chemoradiotherapy group

EXPERIMENTAL

The long-course chemoradiotherapy (LC-CRT) arm refers to a preoperative treatment regimen combining normofractionated radiotherapy with concurrent chemotherapy.

Radiation: LCRT; Drug: CAPOX; Drug: PD-1; Drug: Celecoxib

Short-course chemoradiotherapy group

EXPERIMENTAL

The short-course chemoradiotherapy group refers to a preoperative regimen combining hypofractionated radiotherapy with concurrent or sequential chemotherapy .

Radiation: SCRT; Drug: CAPOX; Drug: PD-1; Drug: Celecoxib

Interventions

LCRT RADIATION

50Gy/25Fx

Long-course chemoradiotherapy group

SCRT RADIATION

25Gy/5Fx

Short-course chemoradiotherapy group

CAPOX DRUG

1000mg/m2 bid d1-14

Long-course chemoradiotherapy group; Short-course chemoradiotherapy group

PD-1 DRUG

300mg d1，q3w

Long-course chemoradiotherapy group; Short-course chemoradiotherapy group

Celecoxib DRUG

200mg, bid

Long-course chemoradiotherapy group; Short-course chemoradiotherapy group

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 18-75 years, regardless of gender.
• Pathologically confirmed rectal adenocarcinoma.
• Tumor located ≤10 cm from the anal verge.
• Baseline stage T3-4 and/or N+ (locally advanced disease).
• No evidence of distant metastasis.
• Microsatellite stability (MSS) or proficient mismatch repair (pMMR).
• Karnofsky Performance Status (KPS) ≥70.
• No prior chemotherapy or any other anticancer therapy before enrollment.
• No prior immunotherapy.
• Able to comply with study protocol requirements throughout the study period.
• Signed written informed consent obtained prior to study participation.

You may not qualify if:

• Pregnant or lactating women.
• Individuals with a history of other malignant diseases within the past 5 years, excluding cured skin cancer and cervical carcinoma in situ.
• Individuals with a history of uncontrolled epilepsy, central nervous system diseases, or mental disorders, where the clinical severity (as judged by the investigator) may impair the ability to sign the informed consent form or affect compliance with oral medication.
• Clinically significant (i.e., active) heart disease, including symptomatic coronary heart disease, congestive heart failure of New York Heart Association (NYHA) class II or worse, severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the past 12 months.
• Individuals requiring immunosuppressive therapy for organ transplantation and those on long-term corticosteroid therapy.
• Individuals with autoimmune diseases.
• Individuals with severe, uncontrolled, recurrent infections or other severe, uncontrolled concurrent diseases.
• Baseline blood routine and biochemical parameters not meeting the following criteria: hemoglobin ≥90 g/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelets ≥100×10⁹/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× upper limit of normal (ULN); alkaline phosphatase (ALP) ≤2.5×ULN; serum total bilirubin \<1.5×ULN; serum creatinine \<1×ULN; serum albumin ≥30 g/L.
• Individuals with known dihydropyrimidine dehydrogenase (DPD) deficiency. Individuals with a history of hypersensitivity to any component of the study medications.

Sponsors & Collaborators

• Fudan University: lead
• Anyang Tumor Hospital: collaborator
• Fujian Cancer Hospital: collaborator
• Shandong First Medical University: collaborator
• Yunnan Cancer Hospital: collaborator

Study Sites (5)

Fujian Provincial Cancer Hospital

Fuzhou, Fujian, 350000, China

RECRUITING

Anyang Tumor Hospital

Anyang, Henan, 455100, China

RECRUITING

The First Affiliated Hospital of Shandong First Medical University

Jinan, Shandong, 250014, China

RECRUITING

Yunnan Cancer Hospital

Kunming, 650118, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Dawei Li

CONTACT

+86-021-64175590; li_dawei@fudan.edu.cn

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: PhD

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: September 4, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: September 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)