Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With Simultaneous Integrated Boost Intensity-modulated Radiotherapy in the Treatment of Locally Advanced Rectal Cancer
Overview
- Phase
- Phase 3
- Intervention
- Tislelizumab
- Conditions
- Rectal Neoplasms
- Sponsor
- Yong Zhang,MD
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Complete response rate
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This study aims to evaluate the efficacy and safety of tislelizumab combined with simultaneous integrated boost intensity-modulated radiotherapy in treating locally advanced rectal cancer. To explore a new PD-1 inhibitor adjuvant chemotherapy model combined with radiotherapy to treat locally advanced rectal cancer.
Detailed Description
This is a randomized controlled trial (RCT). Patients with T3-4 in the 8th AJCC stage or positive regional lymph nodes and no distant metastases will be enrolled. Forty-eight patients will be enrolled by inclusion and exclusion criteria. The enrolled patients will be randomly divided into experimental and control groups (twenty-four patients for each group) to receive preoperative neoadjuvant therapy. The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 \~ 4 cycles of XELOX chemotherapy, while receiving complete tislelizumab treatment for at least 4 cycles (21 days per cycle). The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group. The tumor size will be measured in MRI or CT images, and side effects will be recorded. The primary outcome was CR rate (pathological complete response rate and clinical complete response rate), and secondary outcomes were side effects and 3-year OS and DFS.
Investigators
Yong Zhang,MD
First Affiliated Hospital of Guangxi Medical University
First Affiliated Hospital of Guangxi Medical University
Eligibility Criteria
Inclusion Criteria
- •Aged 18 to 70 years.
- •The pathological type of rectal cancer diagnosed by histopathology is adenocarcinoma.
- •Patients with T3-4 in the eighth AJCC stage or positive regional lymph node and no distant metastasis.
- •Having at least one measurable lesion according to RECIST 1.
- •ECOG score 0-
- •Expected survival time ≥6 months.
- •Major organ function is normal, that is, meeting the following criteria: blood routine: HB≥90g/L, ANC≥1.5×109/L, PLT≥80×109/L; Biochemical examination of ALB≥30g/L, TBIL≤1.5 ULN, ALT and AST≤2.5 ULN, plasma Cr≤1.5 ULN or creatinine clearance ≥60 ml/min.
- •Subjects volunteered to join the study, signed the informed consent, had good compliance, and cooperated with follow-up.
Exclusion Criteria
- •Patients have had or currently have other malignant tumors within 5 years.
- •Patients allergic or sensitive to any drug in the study protocol.
- •Patients innate or acquired immune deficiency (e.g. HIV infection).
- •The presence of any active, known or suspected autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, hypophysitis, hyperthyroidism, hypothyroidism, etc.); The subject had vitiligo. Subjects with asthma require bronchodilators for medical intervention.
- •The presence of active infections requiring systemic treatment.
- •The subject has previously received other PD-1 or PD-L1, or CTLA-4 antibody therapy, or other drug therapy targeting immunoregulatory receptor preparations.
- •Unrelieved toxic effects above CTCAE grade 1 due to any previous treatment, excluding alopecia.
- •Patients with a history of myocardial infarction or stroke, unstable angina pectoris, decompensated heart failure or deep vein thrombosis.
- •Patients with long-term untreated wounds or fractures, major surgical operations or severe traumatic injuries, fractures or ulcers within 4 weeks.
- •Pregnant or lactating women.
Arms & Interventions
Experimental arm
The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 \~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).
Intervention: Tislelizumab
Experimental arm
The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 \~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).
Intervention: Capecitabine
Experimental arm
The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 \~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).
Intervention: Oxaliplatin
Experimental arm
The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 \~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).
Intervention: SIB-IMRT
Control arm
The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.
Intervention: Capecitabine
Control arm
The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.
Intervention: Oxaliplatin
Control arm
The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.
Intervention: IMRT
Outcomes
Primary Outcomes
Complete response rate
Time Frame: 12 weeks~18 weeks
Include in pathological complete response rate and clinical complete response rate. MRI/CT will be used for evaluating the carcinoma status. Pathological complete response rate will be evaluated by surgery.
Secondary Outcomes
- Side effects(6monthes, 3years)
- Disease free survival(3 years)
- Overall survival(3 years)