A Single-center, Phase II Study on Efficacy & Safety of SCRT+CAPOX+Serplulimab+Bevacizumab for MSS Rectal Cancer

A Single-Center, Prospective, Phase II Clinical Study to Evaluate the Preliminary Efficacy and Safety of Short-Course Radiotherapy Followed by CAPOX Chemotherapy Combined With Serplulimab and Bevacizumab as Total Neoadjuvant Therapy for MSS-Type, Mid-Low Locally Advanced Rectal Cancer

In a single-center, prospective, phase II study (ClinicalTrials registration number: [to be filled in]) initiated by our center to evaluate the safety and preliminary efficacy of short-course radiotherapy followed by sequential CAPOX chemotherapy combined with serplulimab and bevacizumab as total neoadjuvant therapy for MSS-type mid-low locally advanced rectal cancer, patients with mid-low MSS-type locally advanced rectal adenocarcinoma were enrolled. They received short-course radiotherapy combined with CAPEOX, serplulimab, and bevacizumab as preoperative total neoadjuvant therapy. It is anticipated that 30 subjects with locally advanced rectal cancer will be enrolled between September 2025 and September 2027.

This phase II exploratory study targets patients with locally advanced mid-low MSS/pMMR rectal cancer. It employs short-course radiotherapy combined with CAPEOX, serplulimab, and bevacizumab as preoperative total neoadjuvant therapy, aiming to clarify the efficacy and safety of this new combined radiotherapy, chemotherapy, targeted therapy, and immunotherapy approach, while also assessing the rectal/anal preservation rate and quality of life of patients. After neoadjuvant therapy, patients will undergo imaging and endoscopic evaluations to determine subsequent treatment strategies. Radical surgical resection will be performed on patients after neoadjuvant immunotherapy, followed by further analysis of the pathological complete response (pCR) rate. The primary study endpoint is the pCR rate, and secondary study endpoints include the objective response rate, organ preservation rate, 3-year disease-free survival (DFS), 3-year overall survival (OS), incidence of adverse events, and quality of life scores (EORTC QLQ-C30, EORTC QLQ-CR29, Wexner).

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Cancer (LARC)
• Intervention / Treatment: Radiation: Short-course radiotherapy; Drug: CAPOX chemotherapy; Drug: Targeted therapy with bevacizumab; Drug: Serplulimab immunotherapy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yifei Pan, Master's Degree in Medicine; Phone Number: 86 13506641535; Email: 13506641535@139.com

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Yifei Pan, Master's Degree in Medicine; Phone Number: 86 13506641535; Email: 13506641535@139.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have a desire to preserve the anus and are willing to receive the entire course of neoadjuvant therapy.

  • Aged between 18 and 75 years, with no gender restrictions.

    • Diagnosed via pelvic MRI and rectoscopy with a tumor located ≤10 cm from the anal verge, with a clinical stage of cT3-4N0/+M0, and lymph nodes confined within the mesorectum.

      • Histologically diagnosed with rectal adenocarcinoma; genetic testing indicates MSS or MSI-L, or immunohistochemistry of tumor biopsy indicates pMMR (positive for MSH1, MSH2, MSH6, and PMS2 proteins).

        • ECOG performance status score of 0-1.

          ⑥ No prior antitumor therapy, immunotherapy, anti-angiogenic therapy, or pelvic radiotherapy before inclusion.

          ⑦ Laboratory tests must meet the following criteria: i. White blood cell count ≥3.5×10⁹/L, absolute neutrophil count ≥1.8×10⁹/L, platelet count ≥100×10⁹/L, and hemoglobin ≥100 g/L; ii. INR ≤1.5, and APTT ≤1.5 times the upper limit of normal, or partial thromboplastin time (PTT) ≤1.5 times the upper limit of normal; iii. Total bilirubin ≤1.25 times the upper limit of normal; ALT and AST ≤3 times the upper limit of normal; serum albumin ≥28 g/L; iv. 24-hour creatinine clearance rate ≥50 mL/min or serum creatinine ≤1.5 times the upper limit of normal.

          ⑧ Willing to participate in this study voluntarily, sign the informed consent form, and comply with the scheduled outpatient visits and related procedural requirements to complete follow-up.

Exclusion Criteria:

• In addition to a confirmed diagnosis of rectal cancer, there is a current or past history of active malignant tumors.

  • Patients with metastases to other sites indicated by preoperative staging.

    • Patients with suspicious positive lymph nodes in non-draining areas of the rectum, such as the internal and external iliac lymph nodes, as assessed by preoperative MRI or CT.

      • Patients requiring emergency surgery due to complications such as intestinal obstruction, intestinal perforation, or intestinal hemorrhage.

        • Patients with severe comorbid conditions and an estimated life expectancy of ≤5 years.

          • Patients with known allergies to any components in the study.

            ⑦ Patients who have received immunosuppressive or systemic corticosteroid therapy for immunosuppressive purposes within 30 days prior to the initiation of study treatment.

            ⑧ Patients who have received any other investigational drug treatment (including immunotherapy) or participated in another interventional clinical trial within 30 days prior to screening.

            ⑨ Patients with other factors that may affect the study results or lead to premature termination of the study, such as alcoholism, drug abuse, other severe diseases requiring combined treatment (including psychiatric disorders), and severe laboratory abnormalities.

            ⑩ Patients with congenital or acquired immunodeficiency (such as HIV infection).

            ⑪ Vulnerable populations, including individuals with psychiatric disorders, cognitive impairments, critically ill patients, minors, pregnant women, illiterate individuals, etc.

            ⑫ Other circumstances where, in the investigator's judgment, the patient is deemed unsuitable to participate in the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant chemoradiotherapy combined with ICIs and targeted therapy for MSS-type LARC

Radiation: Short-course radiotherapy; Radiotherapy adopts a short-course regimen, with a dose of 5*5 Gy, administered once daily at 5 Gy per session for a total of 5 consecutive days of irradiation. It is recommended to use three-dimensional 3D-CRT or IMRT techniques. The irradiation fields include: (1) high-risk recurrence areas of the primary tumor, such as the tumor/tumor bed, mesorectal region, and presacral region. For middle and low rectal cancers, the target area should also encompass the ischioanal fossa; (2) regional lymphatic drainage areas, including the lymphatic drainage area along the common iliac vessels within the true pelvis, mesorectal region, lymphatic drainage area along the internal iliac vessels, and obturator lymph node region.; Drug: CAPOX chemotherapy; Chemotherapy with the CAPOX regimen: Capecitabine tablets are available in strengths of 0.5 g/tablet and 0.15 g/tablet; Oxaliplatin for injection is available in a strength of 0.1 g. The chemotherapy protocol is as follows: After a 7-day rest following radiotherapy, on Day 1 (D1), oxaliplatin is administered intravenously at a dose of 130 mg/m² over 2 hours; from Day 1 to Day 14 of each 3-week cycle, capecitabine is taken orally at a dose of 1000 mg/m² twice daily, with each cycle lasting 3 weeks.; Drug: Targeted therapy with bevacizumab; Targeted therapy: On Day 1 (D1) of chemotherapy initiation, bevacizumab will be administered via infusion at a dose of 7.5 mg/kg, with each treatment course lasting 3 weeks, for a total of 6 courses.; Drug: Serplulimab immunotherapy; Immunotherapy: On Day 1 (D1) of chemotherapy initiation, administer 300 mg of serplulimab, with each treatment cycle lasting 3 weeks, for a total of 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR) rate	In tumor specimens obtained from modified neoadjuvant chemoradiotherapy combined with immunotherapy followed by TME surgical resection, no cancer cells or local lymph node metastasis of cancer cells (ypT0N0M0) are observed under a microscope.	After the completion of these cycles, surgical treatment will be scheduled as appropriate (within 1-2 weeks) based on the assessment results. Pathological evaluation of the postoperative specimens will be conducted according to the tumor TRG criteria.

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 26, 2025
• First Submitted That Met QC Criteria: January 11, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 11, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Rectal cancer; neoadjuvant chemoradiotherapy; MSS; locally advanced; Target therapy; neoadjuvant immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: KY2025-443

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No