Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With SIB-IMRT in the Treatment of Locally Advanced Rectal Cancer

Phase 3

Recruiting

• Conditions: Rectal Neoplasms
• Interventions: Drug: Tislelizumab; Drug: Capecitabine; Radiation: IMRT; Drug: Oxaliplatin; Radiation: SIB-IMRT

• Registration Number: NCT06017583
• Lead Sponsor: Yong Zhang,MD

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.

Study Timeline

• Study First Submitted: 2023-08-18
• Study First Submitted QC: 2023-08-27
• Study First Posted: 2023-08-30
• Study Start: 2023-09-01
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-10
• Last Update Posted: 2023-10-11
• Primary Completion: 2024-08-31
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Aged 18 to 70 years.
2. The pathological type of rectal cancer diagnosed by histopathology is adenocarcinoma.
3. Patients with T3-4 in the eighth AJCC stage or positive regional lymph node and no distant metastasis.
4. Having at least one measurable lesion according to RECIST 1.1.
5. ECOG score 0-1.
6. Expected survival time ≥6 months.
7. 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.
8. Subjects volunteered to join the study, signed the informed consent, had good compliance, and cooperated with follow-up.

Exclusion Criteria

1. Patients have had or currently have other malignant tumors within 5 years.
2. Patients allergic or sensitive to any drug in the study protocol.
3. Patients innate or acquired immune deficiency (e.g. HIV infection).
4. 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.
5. The presence of active infections requiring systemic treatment.
6. The subject has previously received other PD-1 or PD-L1, or CTLA-4 antibody therapy, or other drug therapy targeting immunoregulatory receptor preparations.
7. Unrelieved toxic effects above CTCAE grade 1 due to any previous treatment, excluding alopecia.
8. Patients with a history of myocardial infarction or stroke, unstable angina pectoris, decompensated heart failure or deep vein thrombosis.
9. Patients with long-term untreated wounds or fractures, major surgical operations or severe traumatic injuries, fractures or ulcers within 4 weeks.
10. Pregnant or lactating women.
11. Patients with liver and kidney dysfunction.
12. Patients with a history of abuse of psychotropic drugs and unable to abstain or patients with mental disorders.
13. Patients who have participated in clinical trials of other drugs within 4 weeks.
14. Patients with concomitant diseases that, in the judgment of the investigator, seriously endanger the patient's safety or affect the patient's completion of the study.
15. The investigator judged that participation in this study was not conducive to the maximum benefit of the subjects.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental arm	SIB-IMRT	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).
Control arm	IMRT	The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.
Experimental arm	Capecitabine	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).
Control arm	Capecitabine	The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.
Experimental arm	Tislelizumab	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).
Experimental arm	Oxaliplatin	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).
Control arm	Oxaliplatin	The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.

Primary Outcome Measures

Name	Time	Method
Complete response rate	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 Outcome Measures

Name	Time	Method
Side effects	6monthes, 3years	Myelosuppression, radiation enteritis, radiothermitis
Disease free survival	3 years	DFS was calculated from the date of entry into the study to the date of the time from the beginning of randomization to the disease recurrence or progression or death from any cause.
Overall survival	3 years	OS was calculated from the date of entry into the study to the date of death or the last follow-up visit.

Trial Locations

Locations (1)

First Affiliated Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China