TIME in Immunotherapy Combined With nCRT for Rectal Cancer

NCT ID: NCT05507112

Last Updated: 2022-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-20

Study Completion Date

2029-12-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Locally Advanced Rectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Neoadjuvant chemoradiotherapy plus PD-1 inhibitor

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).

Group Type EXPERIMENTAL

PD-1 inhibitor

Intervention Type 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

Capecitabine

Intervention Type DRUG

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

Long-course radiation therapy

Intervention Type RADIATION

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

Neoadjuvant chemoradiotherapy

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).

Group Type ACTIVE_COMPARATOR

Capecitabine

Intervention Type DRUG

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

Long-course radiation therapy

Intervention Type RADIATION

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

Interventions

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PD-1 inhibitor

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

Intervention Type DRUG

Capecitabine

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

Intervention Type DRUG

Long-course radiation therapy

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

Intervention Type RADIATION

Other Intervention Names

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Tislelizumab Xeloda

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years and ≤75 years on the day of signing informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
3. Histologically proven rectal adenocarcinoma.
4. \<12 cm from anal verge.
5. Clinical stage of T3/T4 or N positive and M0
6. No previous chemotherapy, radiotherapy, immunotherapy or surgical treatment
7. 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.
8. Adequate hepatic and renal function to chemoradiotherapy, immunotherapy and surgery.
9. Willing and able to provide written informed consent.

Exclusion Criteria

1. Allergic to any component of chemotherapy or immunotherapy;
2. Patients with multiple primary colorectal cancer;
3. 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;
4. Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, or other conditions requiring emergency surgical resection;
5. Prior or planed organ/bone marrow transplant
6. Patients who receive systemic steroid therapy or immunosuppressive agents within 30 days before enrollment in the study;
7. Pregnant or lactating women
8. Patients with a history of severe mental illness or being unable to comply with the research protocols.
9. Patients who have contraindications to chemoradiotherapy, immunotherapy or surgery.
10. Patients who have any other conditions that investigator judges unsuitable to participate.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking Union Medical College Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jiaolin Zhou, Ph.D

Role: STUDY_CHAIR

Peking Union Medical College Hospital

Central Contacts

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Jiaolin Zhou, Ph.D

Role: CONTACT

+86-13910136704

Other Identifiers

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PUMCH_TIMENT-R

Identifier Type: -

Identifier Source: org_study_id

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