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NCT Number: NCT05507112

TIME in Immunotherapy Combined With nCRT for Rectal Cancer

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.

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Key information

Conditions

Locally Advanced Rectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Rectal Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

About this study

Objectives:

  • 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.
  • To clarify the effect of nCRT on TIME for rectal cancer, and the further effect of adding Immunotherapy.
  • 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.
  • To clarify the potential mechanism of immune response or immune escape to neoadjuvant immunotherapy for LARC patients.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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

Other names: Tislelizumab

Capecitabine

Drug

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

Other names: Xeloda

Long-course radiation therapy

Radiation

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

Primary outcomes

  1. Complete response rate (CR rate)

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

    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.

Secondary outcomes

  1. Pathological tumor regression grade (CAP)

    Time frame: 1-2 weeks after surgery

    All tumor tissues will be analyzed by experienced pathologists. Determination of tumor regression will adopt College of American Pathologists (CAP) tumor regression grade, which are as follows: CAP0: No viable cancer cells (complete response); CAP1:Single cells or rare small groups of cancer cells (near complete response); CAP2: Residual cancer with evident tumor regression, but more than single cells or rare small groups of cancer cells (partial response); and CAP3: Extensive residual cancer with no evident tumor regression (poor or no response).

  2. Rate of tumor down-staging

    Time frame: 1-2 weeks after surgery

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

  3. Lymphocytes infiltration changes after treatment

    Time frame: 2 weeks before treatment and 1-2 weeks after surgery

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

  4. The expression of immune-related pathways

    Time frame: 2 weeks before treatment and 1-2 weeks after surgery

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

  5. Rectal MRI defined tumor regression

    Time frame: Baseline and 1 week before surgery

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

  6. Rectal MRI defined tumor down-staging

    Time frame: Baseline and 1 week before surgery

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

  7. Rectal MRI defined tumor volume change

    Time frame: Baseline and 1 week before surgery

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

  8. Local recurrence (LR) rate

    Time frame: 3, 5 years

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

  9. Disease free survival (DFS)

    Time frame: 3, 5 years

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

  10. Disease-related Treatment Failure (DrTF) rate

    Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60

    DrTF was defined as the time from the initiation of radiotherpay to the date of each of the following, whichever occurred first: disease progression during/after treatment, distant metastasis at any timepoint, or death from any cause.

  11. Overall survival (OS)

    Time frame: 3, 5 years

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

  12. Surgical complications

    Time frame: The surgical complications are assessed up to 5 years from the surgery

    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".

  13. R0 resection rate

    Time frame: Within two weeks after surgery

    Rate of complete tumor removal with negative microscopically resection margin.

  14. Rate of sphincter-sparing surgery

    Time frame: Within two weeks after surgery

    Rate of sphincter-sparing surgery if surgery is performed.

  15. Rate of adverse event

    Time frame: From date of randomization until the date of death from any cause, assessed up to 5 years

    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.

  16. Patient reported outcome: Quality of life according to questionnaire European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) (v 3.0)

    Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60

    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.

  17. Patient reported outcome: Quality of life according to questionnaire European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29)

    Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60

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

  18. Patient reported outcome: Functional outcome according to Wexner score

    Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60

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

Sponsors and collaborators

Lead sponsor

Peking Union Medical College Hospital

Other

Registry information

Official study title

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

Acronym: TIMENT-R

Important dates

Study start
2022
Primary completion
2025
Study completion
2029
First posted
Aug 18, 2022
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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