Neoadjuvant Chemoradiotherapy Combined With Immunotherapy and Anti-angiogenesis in Treating Locally Advanced Rectal Cancer

NCT07134218 | Not Yet Recruiting Phase 2

• 1 other identifier: CHOICE IV
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, prospective, randomized phase II trial designed to evaluate the efficacy and safety of short-course neoadjuvant chemoradiotherapy combined with the PD-1 monoclonal antibody serplulimab and the anti-angiogenic agent bevacizumab in patients with previously untreated pMMR/MSS middle and low locally advanced rectal cancer. The study plans to enroll a total of 200 participants (100 in the experimental arm and 100 in the control arm).

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• The rate of cCR

  Rate of patients who achieve clinical complete response

  2 years

Secondary Outcomes (8)

• Major Pathological Response

  2 years

• Objective Response Rate

  2 years

• Disease-Free Survival (DFS)

  2 years

• Overall Survival (OS)

  2 years

• Organ Preservation Rate (OPR)

  2 years

Study Arms (2)

neoadjuvant chemoradiation therapy + serplulimab + bevacizumab

EXPERIMENTAL

Drug: serplulimab、bevacizumab

neoadjuvant chemoradiation therapy

OTHER

Drug: serplulimab、bevacizumab; Other: neoadjuvant chemoradiation therapy

Interventions

serplulimab、bevacizumab DRUG

short-course radiotherapy 25 Gy in 5 fractions → 2-week break → 2 cycles of FOLFOX + serplulimab + bevacizumab → 2 cycles of FOLFOX + serplulimab.

neoadjuvant chemoradiation therapy; neoadjuvant chemoradiation therapy + serplulimab + bevacizumab

neoadjuvant chemoradiation therapy OTHER

short-course radiotherapy 25 Gy in 5 fractions → 2-week break → 4 cycles of FOLFOX alone.

neoadjuvant chemoradiation therapy

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent to voluntarily participate in the study;
• Aged 18 to 75 years, inclusive, regardless of sex;
• Histologically confirmed rectal adenocarcinoma with immunohistochemistry results showing proficient mismatch repair (pMMR) or molecular testing results indicating microsatellite stability (MSS);
• Clinical baseline staging assessed by MRI as T3-4N0M0/TanyN+M, with negative mesorectal fascia (MRF);
• Tumor lower margin ≤7 cm from the anal verge;
• Surgically resectable;
• Capable of swallowing tablets normally;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1;
• No prior anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, or surgery;
• Planned to undergo surgical treatment after completion of neoadjuvant therapy;
• No contraindications to surgery;
• Normal function of major organs.

You may not qualify if:

• History of allergy to any component of bevacizumab, serplulimab, 5-FU, or oxaliplatin.
• Prior or ongoing treatment with any of the following:
• Any tumor-targeted surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
• Immunosuppressive drugs or systemic corticosteroid therapy for immunosuppressive purposes within 2 weeks before the first administration of the study drug (dose \> 10 mg/day prednisone or equivalent). Inhaled or topical corticosteroids and adrenal corticosteroid replacement therapy (dose \> 10 mg/day prednisone or equivalent) are permitted in the absence of active autoimmune disease.
• Live-attenuated vaccine within 4 weeks before the first administration of the study drug.
• Major surgery or severe trauma within 4 weeks before the first administration of the study drug.
• History of immunodeficiency, including HIV positivity, or other acquired or congenital immunodeficiency diseases, or history of organ transplant or allogeneic bone marrow transplant.
• Uncontrolled cardiac symptoms or diseases, including but not limited to: (1) NYHA class II or higher heart failure, (2) unstable angina, (3) myocardial infarction within the past year, (4) clinically significant supraventricular or ventricular arrhythmias that are not controlled or remain poorly controlled after clinical intervention.
• Severe infection (CTCAE \> grade 2) within 4 weeks before the first administration of the study drug, such as severe pneumonia, bacteremia, or infection with complications requiring hospitalization. Baseline chest imaging showing active pulmonary inflammation, or presence of signs and symptoms of infection or need for oral or intravenous antibiotic therapy within 14 days before the first administration of the study drug (excluding prophylactic antibiotic use). History of active pulmonary tuberculosis infection identified through medical history or CT scan, or history of active pulmonary tuberculosis infection within the past year, or history of active pulmonary tuberculosis infection more than 1 year ago that was not properly treated.
• Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL), hepatitis C (positive HCV antibody and HCV RNA above the lower limit of detection of the assay).
• Pregnant or breastfeeding women.
• Presence of other factors that, in the investigator's judgment, may lead to forced discontinuation of the study, such as other severe diseases (including psychiatric conditions) requiring concomitant treatment, alcoholism, drug abuse, family or social factors that may affect the participant's safety or compliance.

Sponsors & Collaborators

• Changhai Hospital: lead

Study Sites (1)

Department of Colorectal Surgery in Changhai Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Neoadjuvant Therapy

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: August 21, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 2 years

Locations

CN (1)