Clinical trial NCT05507112: TIME in Immunotherapy Combined With nCRT for Rectal Cancer
Official title: The Therapeutic and Prognostic Implications of Tumor Immune Microenvironment in The Neoadjuvant Immunotherapy Combined With Chemoradiotherapy for Rectal Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Keywords: Rectal Cancer
Immunotherapy
neoadjuvant therapy
Tumor Immune Microenvironment
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2022-08-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathological complete response (pCR) rates
timeFrame: 1-2 weeks after surgery
Secondary outcomes:
measure: Major pathological response (MPR) rates
timeFrame: 1-2 weeks after surgery
measure: Pathological tumor regression grade (TRG)
timeFrame: 1-2 weeks after surgery
measure: Rate of tumor down-staging
timeFrame: 1-2 weeks after surgery
measure: Lymphocytes infiltration changes after treatment
timeFrame: 2 weeks before treatment and 1-2 weeks after surgery
measure: The expression of immune-related pathways
timeFrame: 2 weeks before treatment and 1-2 weeks after surgery
measure: Rectal MRI defined tumor regression
timeFrame: Baseline and 1 week before surgery
measure: Rectal MRI defined tumor down-staging
timeFrame: Baseline and 1 week before surgery
measure: Rectal MRI defined tumor volume change
timeFrame: Baseline and 1 week before surgery
measure: Local recurrence(LR) rate
timeFrame: 3, 5 years
measure: Disease free survival (DFS)
timeFrame: 3, 5 years
measure: Overall survival (OS)
timeFrame: 3, 5 years
measure: Surgical complications
timeFrame: The surgical complications are assessed up to 5 years from the surgery
measure: R0 resection rate
timeFrame: Within two weeks after surgery
measure: Rate of sphincter-sparing surgery
timeFrame: Within two weeks after surgery
measure: Rate of adverse event
timeFrame: From date of randomization until the date of death from any cause, assessed up to 5 years
measure: 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)
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60
measure: 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)
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60
measure: Patient reported outcome: Functional outcome according to Wexner score
timeFrame: Baseline and months 3, 6, 12, 24, 36, 60
Other outcomes:
Locations:
Study officials:
affiliation: Peking Union Medical College Hospital
name: Jiaolin Zhou, Ph.D
role: STUDY_CHAIR
References: