Neoplasms

Digestive System Diseases

All Conditions

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Tislelizumab

Immunomodulating Agents

Immune Checkpoint Inhibitors

Antimetabolites

Antineoplastic Agents, Immunological

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).

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).

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

PD-1 inhibitor

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

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

Long-course radiation therapy

Jiaolin Zhou, Ph.D

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 end point is the rate of pathological complete response (pCR). The long-term prognosis and adverse effects will also be evaluated and analyzed.

Objectives:

1. To clarify the efficacy and safety of combined therapy for locally advanced rectal cancer (LARC) patients and verify the efficacy and safety of neoadjuvant immunotherapy for dMMR/MSI-H LARC patients.
2. To clarify the effect of nCRT on TIME for rectal cancer, and the further effect of adding Immunotherapy.
3. To verify the feasibility of predicting the efficacy of combined therapy by the infiltration level of CD8+ PD1+ TILs in tumor tissue before treatment in pMMR/MSS LARC patients and explore the comprehensive prediction index of the efficacy of combined therapy for LARC patients.
4. To clarify the potential mechanism of immune response or immune escape to neoadjuvant immunotherapy for LARC patients.

TIME in Immunotherapy Combined With nCRT for Rectal Cancer

The Therapeutic and Prognostic Implications of Tumor Immune Microenvironment in The Neoadjuvant Immunotherapy Combined With Chemoradiotherapy for Rectal Cancer

Proportion of patients who achieve a pathological complete response following treatment

The proportion of patients experiencing a major pathological response to neoadjuvant treatment.

TRG is evaluated according to the AJCC system. TRG0-1 is defined as good response, TRG2 as moderate response, and TRG3 as poor response.

The proportion of patients experiencing tumor down-staging will be assessed by pathology.

The categories, number and distribution of lymphocytes infiltrated in tumor and tumor stroma are measured by Multiplex immunofluorescence assay.

The expression of immune-related pathways is measured by RNAseq.

Proportion of patients achieving rectal MRI-confirmed near or complete tumor regression.

Proportion of patients achieving rectal MRI-confirmed down-staging.

The change of patients' tumor volume will be confirmed by rectal MRI.

Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology

The three-year and five-year disease-free survival of patients.

The three-year and five-year overall survival of patients.

Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc, which will also be assessed according to "Clavien-Dindo Classification of surgical complications".

Rate of complete tumor removal with negative microscopically resection margin.

Rate of sphincter-sparing surgery if surgery is performed.

Rate of adverse events will be assessed according to National Cancer Institution Common Terminology Criteria of Adverse Events (NCI-CTCAE) v.4.02. Adverse events of this trial will include immune-related adverse events, chemo- and radiotherapy related adverse events, and combined treatment-related adverse events.

Score values from 1 (not at all) to 4 (very much) respectively from 1 (very poor) to 7 (excellent). Score outcome depends on score type.

Score values from 1 (not at all) to 4 (very much). Score outcome depends on score type.

Five score values from "never" to "1 per day or more often". The more often the worse outcome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
TIME in Immunotherapy Combined With nCRT for Rectal Cancer	NCT05507112	Locally Advance...	PD-1 inhibitor Capecitabine Long-course rad...	18 Years - 75 Years	Peking Union Medical College Hospital
TIME in Immunotherapy Combined With nCRT for Rectal Cancer	NCT05507112	Locally Advance...	PD-1 inhibitor Capecitabine Long-course rad...	18 Years - 75 Years	Peking Union Medical College Hospital

Spots Global Cancer Trial Database for tumor immune microenvironment