Neoadjuvant Chemoradiotherapy Plus Sintilimab for MSS, Locally Advanced Rectal Cancer-

NCT06895577 | Withdrawn Phase 2 DMC

• 1 other identifier: GIHSYSU-37
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This research investigates the efficacy and safety of combining Sintilimab, a PD-1 inhibitor, with neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced microsatellite-stable (MSS) rectal cancer. Given the limitations of current treatment strategies in achieving optimal clinical outcomes, this prospective, single-center, phase II clinical trial aims to improve pathological complete response (pCR) rates and overall survival (OS). The primary endpoint is pCR, with secondary endpoints including disease-free survival (DFS) and the incidence of treatment-related adverse events. This study seeks to provide insights into a novel treatment paradigm for MSS locally advanced rectal cancer, potentially offering improved therapeutic options for this patient population.

Conditions

Rectal Cancer

Keywords

Rectal cancer; PD-1; neoadjuvant chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  Pathological complete response will be evaluated with American Joint Committee on Cancer (AJCC) Cancer Staging

  1 month after the surgery

Secondary Outcomes (5)

• Margin-free (R0) resection rate

  Immediately after the surgery

• Tumor regression grade

  1 month after surgery

• Number of participants with surgical complications

  30 days after surgery

• 3-year event-free survival rate

  3-year event-free survival rate

• Local recurrence

  3 years after the surgery

Study Arms (1)

neoadjuvant SCRT followed by Sintilimab plus CAPOX

EXPERIMENTAL

neoadjuvant SCRT followed by Sintilimab plus CAPOX

Drug: neoadjuvant SCRT followed by Sintilimab plus CAPOX

Interventions

neoadjuvant SCRT followed by Sintilimab plus CAPOX DRUG

SCRT (a total of 25 Gy in 5 days) followed by sintilimab (3mg/kg intravenous drip on day 1; every 3-week cycle for two cycles) combined with CAPOX (oxaliplatin 130 mg/m2 intravenous infusion over 2 h on day 1, capecitabine 1000 mg/m2 orally twice daily from day 1-14, in every 3-week cycle for two cycles) 1 week later.

neoadjuvant SCRT followed by Sintilimab plus CAPOX

Eligibility Criteria

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

You may qualify if:

• With my consent and signed informed consent, willing and able to comply with the planned visits, research treatment, laboratory tests, and other test procedures.
• Age 18-75. Patients with a pathologically or cytologically confirmed adenocarcinoma of the rectum, all other histological types excluded.
• The distance between the lower margin of the rectal tumor lesion and the anal margin \<12 cm.
• The physical status score (ECOG) of the Eastern Cooperative Oncology Group was 0-1 (see Appendix 1).
• T3-4/N+ was evaluated by pelvic enhanced MRI. Had not received systemic anti-tumor therapy for colon cancer, including cytotoxic drugs, immune checkpoint inhibitor therapy, molecular targeted therapy, endocrine therapy, etc.
• Appropriate organ function based on the following laboratory test values obtained during the screening period: white blood cell count ≥3 × 10\^9/L, neutrophil count ≥1.5 × 10\^9/L, platelet count ≥75 × 10\^9/L, serum total bilirubin ≤1.5 × upper limit of normal (UNL), AST (SGOT) or ALT (SGPT) ≤2.5 × UNL, serum creatinine ≤1.5 × UNL.
• Female subjects of reproductive age must undergo a negative serum pregnancy test within 3 days prior to the start of the study drug and be willing to use a medically approved highly effective contraceptive method (such as an IUD, contraceptive pill, or condom) during the study period and within 3 months after the last study drug administration; male subjects whose partners are women of reproductive age should be surgically sterilized or agree to use effective contraception during the study period and for 3 months after the last study dosing.
• Willing and able to comply with research procedures and visit plans.

You may not qualify if:

• Whole-body CT, MRI, or PET-CT confirms distant metastases (M1). Patients with complete intestinal obstruction, active bleeding, or perforation requiring emergency surgery.
• The presence of other active malignancies in the past or at the same time (except malignancies that have received curative treatment and have been free of disease for more than 5 years or cancers in situ that can be cured by adequate treatment).
• Thrombotic or embolic events (e.g., cerebrovascular accident, including transient ischemic attack, pulmonary embolism, and deep vein thrombosis) occurred in the 12 months prior to study entry.
• Myocardial infarction, severe/unstable angina pectoris, NYHA grade 2 or higher cardiac dysfunction, clinically significant supraventricular or ventricular arrhythmia, and symptomatic congestive heart failure in the 12 months prior to enrollment.
• Systemic antibiotic use ≥7 days within 4 weeks prior to enrollment, or unexplained fever \>38.5°C during screening or prior to first dosing (fever due to tumor could be included).
• Had received major operations such as laparotomy, thoracotomy, laparoscopic resection of organs, or severe trauma within 2 months before enrollment (the surgical incision should be completely healed before enrollment in this clinical trial).
• Known presence of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related disease.
• The presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
• Untreated active hepatitis (hepatitis B defined as HBV-DNA ≥500 IU/ml; hepatitis C defined as HCV-RNA above the lower detection limit of analytical methods) or co-infection with hepatitis B and hepatitis C.
• A known or suspected history of allergy to any of the relevant drugs used in the study.
• Pregnant or lactating women. Women of reproductive age who do not use effective non-hormonal contraception (or refuse to use it) or men who are likely to have children.
• The presence of other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of participating in the study or interfere with the study results, as well as patients deemed unsuitable for participation in this study by the investigator.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Department of colorectal surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangzhou, 510000, 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 19, 2025
• First Posted: March 26, 2025
• Study Start: June 20, 2025
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)