Chemotherapy and Tislelizumab With Split-course HFRT for Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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The question of how to administer adequate chemotherapy and immunotherapy to synchronise hypofraction radiotherapy （HFRT） treatment strategy to maximise the benefits of neoadjuvant therapy for the improved prognosis of patients with locally advanced rectal cancer (LARC).We aimed to study whether chemotherapy and tislelizumab plus split-course HFRT results in better outcomes in LARC patients.

Detailed Description
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Prior to analyzing continuous variables, the statistical normality of the data will be determined. The differences between the main variables will be compared by using the analysis of variance. A comparison of data on categorical variables will be carried out by χ2 tests or Fisher's exact tests. The OS and PFS was estimated using the Kaplan-Meier method. PFS and OS will be compared using the log-rank test. In cases where variables must be adjusted, we will use the proportional hazard Cox regression model. P values for all analyses will be based on using a significance level of 0.05.

Official Title
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Combined Chemotherapy and Tislelizumab With Preoperative Split-course Hypofraction Radiotherapy for Locally Advanced Rectal Cancer:Study Protocol of a Prospective, Single-arm Phase II Trial

Conditions
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Rectal Cancer, Radiation Oncology

Intervention / Treatment
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* Radiation: split-course HFRT
* Drug: CAPOX chemotherapy
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment-naïve patients with operable locally advanced cancer (LARC, T3-4 and/or N+) Pathologically diagnosed as rectal adenocarcinoma Male or non-pregnant female Age: 18-70 years old Hematology examination：I. White blood cell count ≥4×10^9/L;II. Neutrophils ≥1.5×10^9/L;III. Platelet count ≥100×10^9/L;IV. Hemoglobin ≥9g/L Blood biochemical examination: total bilirubin, AST, ALT≤2.0×upper limit of normal; creatinine≤1.5×upper limit of normal Functional status: ECOG score 0-1 points or KPS score ≥70 points Obtain the patient's informed consent Exclusion Criteria: Pathologically diagnosed as non-adenocarcinoma Age> 70 years old Patients with recurrence and distant metastasis Have a history of other malignancies Have had radiotherapy and/or chemotherapy Pregnant or breastfeeding women Mentally disordered Patients with severe heart, liver, and kidney damage Non-compliance or the investigator believes that the patient cannot complete the entire trial treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HFRT with concurrent chemotherapy and immunotherapy<br>CAPOX chemotherapy plus tislelizumab treatment plus split-course HFRT | Radiation: split-course HFRT<br>* 7Gy/F, d7, q3w, 5 cycles<br>* Other names: hypofraction radiotherapy;Drug: CAPOX chemotherapy<br>* CAPOX chemotherapy will commence on day 1 for each of six cycles: oxaliplatin 130 mg/m^2 intravenous infusion on day 1,followed by capecitabine 1000 mg/m^2 administered orally twice daily on day 1 to 14 of a 21-day cycle.<br>* Other names: oxaliplatin and capecitabine;Drug: Tislelizumab<br>* Tislelizumab 200 mg intravenous infusion on day 1 of each 21-day cycle for each of six cycles.<br>* Other names: immunotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete response(pCR) | pCR is defined as no residual tumor in the surgical specimen. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year disease-free survival | the time from randomization to disease recurrence or patient death due to disease progression. | 2 years | 
| local recurrence rate | It's defined as disease-free proximal, distal and circumferential margins.And its progression was defined as an increase in tumor size. | 3 years | 
| overall survival(OS) | It's defined as the time after the first dose of study therapy to death from any cause. | 5 years | 
| Sphincter-sparing surgery rate | sphincter-sparing surgery rate | 1 year | 
| R0 Resection Rate(R0-R) | It's defined as the percentage of patients undergoing resection, defined as a tumour-free resection margin. | 1 year | 
| predictive biomarkers andquality of life(QoL) | Objective condition index include subjective perception index objective condition index and subjective perception index. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemotherapy, tislelizumab, split-course hypofraction radiotherapy, locally advanced rectal cancer