TIME in Immunotherapy Combined With nCRT for Rectal Cancer (TIMENT-R)

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Active, not recruiting; Phase 2

Conditions: Locally Advanced Rectal Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05507112

PUMCH_TIMENT-R

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Neoadjuvant chemoradiotherapy plus PD-1 inhibitor

Experimental group

Description:

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).

Treatment:

Drug: PD-1 inhibitor

Radiation: Long-course radiation therapy

Drug: Capecitabine

Neoadjuvant chemoradiotherapy

Active Comparator group

Description:

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).

Treatment:

Radiation: Long-course radiation therapy

Drug: Capecitabine