TIME in Immunotherapy Combined With nCRT for Rectal Cancer

NCT05507112 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: PUMCH_TIMENT-R
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, prospective phase II clinical trial to evaluate the therapeutic and prognostic implications of tumor immune microenvironment in the neoadjuvant immunotherapy combined with chemoradiotherapy for patients with rectal cancer. A total of 100 patients will be enrolled in this trial. The primary endpoint is the complete response rate, defined as the proportion of patients who achieve pathological complete response (pCR) or clinical complete response (cCR) without evidence of distant metastasis on post-treatment or preoperative assessment. The long-term prognosis and adverse effects will also be evaluated and analyzed.

Conditions

Locally Advanced Rectal Cancer

Keywords

Rectal Cancer; Immunotherapy; neoadjuvant therapy; Tumor Immune Microenvironment

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CR rate)

  Proportion of patients who achieve pathological complete response (pCR) or clinical complete response (cCR) without evidence of distant metastasis on post-treatment or preoperative assessment.

  1-2 weeks after surgery or assessment after termination of neoadjuvant treatment

Secondary Outcomes (18)

• Pathological tumor regression grade (CAP)

  1-2 weeks after surgery

• Rate of tumor down-staging

  1-2 weeks after surgery

• Lymphocytes infiltration changes after treatment

  2 weeks before treatment and 1-2 weeks after surgery

• The expression of immune-related pathways

  2 weeks before treatment and 1-2 weeks after surgery

• Rectal MRI defined tumor regression

  Baseline and 1 week before surgery

Study Arms (2)

Neoadjuvant chemoradiotherapy plus PD-1 inhibitor

EXPERIMENTAL

Capecitabine 1650mg/m2 is given 5 days a week in parallel with radiotherapy 45 to 50 Gy during 5 consecutive weeks. Tislelizumab is given on day 1 of week 2, 5 and 8 at 200 mg i.v. 8-12 weeks after completion of radiation therapy, patients undergo total mesorectal excision (TME). If the investigator and the subject opt for a "watch-and-wait" strategy after completing neoadjuvant therapy, a one-year follow-up will be conducted. If no additional surgery is performed due to disease-related reasons by the end of the follow-up period, this outcome is recognized as a clinical complete response (cCR).

Drug: PD-1 inhibitor; Drug: Capecitabine; Radiation: Long-course radiation therapy

Neoadjuvant chemoradiotherapy

ACTIVE COMPARATOR

Capecitabine 1650mg/m2 is given 5 days a week in parallel with radiotherapy 45 to 50 Gy during 5 consecutive weeks. 8-12 weeks after completion of radiation therapy, patients undergo total mesorectal excision (TME).

Drug: Capecitabine; Radiation: Long-course radiation therapy

Interventions

PD-1 inhibitor DRUG

Tislelizumab (3 cycles): 200mg i.v. q3w on day 1 of each cycle, and starting from the second week after the start of radiotherapy

Also known as: Tislelizumab

Neoadjuvant chemoradiotherapy plus PD-1 inhibitor

Capecitabine DRUG

Capecitabine 1650mg/m2/d orally twice-daily, 5 days a week for a total of 5 weeks.

Also known as: Xeloda

Neoadjuvant chemoradiotherapy; Neoadjuvant chemoradiotherapy plus PD-1 inhibitor

Long-course radiation therapy RADIATION

45-50 Gy/day, 5 days a week for a total of 5 weeks.

Neoadjuvant chemoradiotherapy; Neoadjuvant chemoradiotherapy plus PD-1 inhibitor

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 years and ≤75 years on the day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Histologically proven rectal adenocarcinoma.
• \<12 cm from anal verge.
• Clinical stage of T3/T4 or N positive and M0
• No previous chemotherapy, radiotherapy, immunotherapy or surgical treatment
• No immune system disease (e. g. systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis, scleroderma, mixed connective tissue disease, dermatomyositis (DM), hyperthyroidism, hypothyroidism, ulcerative colitis (UC), autoimmune hemolytic anemia (AIHA) or human immunodeficiency virus (HIV) infection.
• Adequate hepatic and renal function to chemoradiotherapy, immunotherapy and surgery.
• Willing and able to provide written informed consent.

You may not qualify if:

• Allergic to any component of chemotherapy or immunotherapy;
• Patients with multiple primary colorectal cancer;
• Other malignant tumors within 5 years, except for adequately treated cervical carcinoma in situ or cutaneous basal cell carcinoma, or basically controlled localized prostate cancer or surgically excised ductal carcinoma in situ of breast;
• Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, or other conditions requiring emergency surgical resection;
• Prior or planed organ/bone marrow transplant
• Patients who receive systemic steroid therapy or immunosuppressive agents within 30 days before enrollment in the study;
• Pregnant or lactating women
• Patients with a history of severe mental illness or being unable to comply with the research protocols.
• Patients who have contraindications to chemoradiotherapy, immunotherapy or surgery.
• Patients who have any other conditions that investigator judges unsuitable to participate.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Immune Checkpoint Inhibitors; tislelizumab; Capecitabine

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)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jiaolin Zhou, Ph.D

  Peking Union Medical College Hospital

  STUDY CHAIR

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: July 17, 2022
• First Posted: August 18, 2022
• Study Start: December 20, 2022
• Primary Completion: May 30, 2025
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 7, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)