Neoadjuvant Long-course Chemoradiotherapy Followed by Immunotherapy for Locally Advanced Mid-low Rectal Cancer (NLCCRIT-LARC)

Neoadjuvant Long-course Chemoradiotherapy Followed by PD-1 Monoclonal Antibody for Locally Advanced Mid-low Rectal Cancer

The purpose of this study was to evaluate the effect of capecitabine-based long-term radiotherapy followed by 3 cycles Sintilimab (PD-1 inhibitor) in patients with locally advanced rectal cancer.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Radiation: radiation; Drug: PD-1 Monoclonal Antibody; Procedure: TME surgery

Detailed Description

Investigator designed a single-arm, open-label, phase II trial and the purpose of this study is to observe and evaluate the efficacy and safety of capecitabine-based long-term radiotherapy followed by 3 cycles Sintilimab (PD-1 inhibitor) for locally advanced rectal cancer.Participants will accept capecitabine-based long-term radiotherapy(50.4Gy radiation) followed by 200mg Sintilimab each time for 3 times, with 2-week intervals. The primary endpoint is pCR rate, and secondary endpoints include sphincter-preserving rate, adverse event rates.

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

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100044
      • Peking University People's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• aged 18~75
• ECOG score 0~2
• biopsy diagnosed rectal adenocarcinoma, distal margin within 10cm to anal verge
• no distant metastasis, staged II/III (T4b excluded) by MRI
• maximum diameter of rectal cancer lesion≥10mm according to baseline CT or MR
• willing and able to comply with study protocol
• consent to the use of blood and tissue specimens for study
• no history of previous anti-tumor treatment (e.g. radiation, chemo, immuno, bio, herbal, etc.)
• no disorders/diseases of immune system (e.g. systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, autoimmune hemolytic anemia, hyperthyroidism/hypothyroidism, ulcerative colitis, autoimmune hemolytic anemia, HIV infection, etc.)
• no significant dysfunction of major viscera (e.g. heart, lung, liver, kidney, etc.)
• no jaundice or gastrointestinal obstruction
• no acute/ongoing infection
• no significant irregularities in blood routine test and biochemical test results, particular requirements include: neutrophils≥1.5×109/L, HGB≥80g/L, platelet≥100×109/L, serum creatinine≤1.5×ULN, total bilirubin≤1.5×ULN, ALT、AST≤2.5×ULN
• no social or mental disorder
• for women of child-bearing age, a negative result of serological pregnancy test is required, and effective contraception measures from inclusion till 60 days after the last dose of study drug is required

Exclusion Criteria:

• multiple cancers, or with concomitant malignant tumors besides rectal cancer
• having received any anti-cancer treatment (surgery, drugs, etc.) in the past 5 years
• history of recent major surgery
• with condition that affects the absorption of capecitabine via gastrointestinal tract (e.g. inability to swallow, nausea, vomiting, chronic diarrhea, etc.)
• with uncontrolled, severe, concomitant diseases of any sort
• allergic to any of the ingredients under study
• estimated survival ≤ 5 years due to any reason
• preparing for or having previously received organ or bone marrow transplant
• having received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to inclusion
• for patients with history of disorder of central nervous system, investigator discretion is required as to whether the clinical severity prevents the signing of informed consent or affects the patient or oral medication compliance
• with other conditions/issues that may affect the study results or cause the study treatment to be terminated halfway (e.g. alcoholism, drug abuse, etc.)
• pregnant or lactating women, or women intending on conception during treatment period

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: nCRT+PD-1; Long-course chemoradiation followed by PD-1 inhibition (Sintilimab 200mg, 3 times, 2-week interval) starting on Day 15 after completion of radiation therapy. TME surgery is scheduled in 6 weeks after completion of radiation.	Radiation: radiation; 45 Gy radiation dose in 25 fractions to the pelvis; Drug: PD-1 Monoclonal Antibody; 200mg Sintilimab after radiation (3 times, 2-week interval); Other Names: Sintilimab; Procedure: TME surgery; TME surgery for 6~8 weeks after radiation; Other Names: radical proctectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	pathological complete response rate	within 1 week after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sphincter preserving rate	proportion of patients with preserved anal sphincter	instantly after surgery
immune-related adverse event rate	adverse event rate that is deemed to be associated with PD-1 inhibition	from commencing of PD-1 inhibition to the 30th day after surgery
treatment-related adverse event rate	adverse event rate that is deemed to be associated with all treatments	from commencing of treatment to the 30th day after surgery
incidence rate of surgical complications	incidence rate of surgical complications within 30 days after surgery	within 30 days after surgery

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Zhanlong Zhanlong, M.D., Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Actual): April 1, 2025
• Study Completion (Actual): April 1, 2025

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: neoadjuvant therapy; Locally Advanced Rectal Cancer; PD-1 inhibition
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physical Phenomena; Radiation; sintilimab; spartalizumab
• Other Study ID Numbers: 2023PHB222; Z220014 (Other Grant/Funding Number: Beijing Municipal Natural Science Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Export of individual patient data is a sensitive issue according to current Chinese laws

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