Tislelizumab Combined With Concurrent Chemoradiotherapy as First-line Treatment for Stage IIIC2 Cervical Cancer

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in first-line treatment of stage IIIC2 cervical cancer.

Detailed Description
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This is a multicenter, prospective, and randomized phase II clinical trial. Patients assigned to experimental group will receive standard radiotherapy with concomitant cisplatin 40mg/m2 once every week for 5 weeks, combined with tislelizumab (200 mg, day 1) once every 3 weeks until disease progression or intolerable toxicity occurs or one year. Patients assigned to control group will undergo standard radiotherapy with concomitant cisplatin 40mg/m2 once every week for 5 weeks. Compare the efficacy and toxicity of the two regimens in patients with stage IIIC2 cervical cancer.

Official Title
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Efficacy and Safety of Tislelizumab Combined With Concurrent Chemoradiotherapy as First-line Treatment for Stage IIIC2 Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: tislelizumab
* Other: concurrent chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: (1)18-70 years old; (2)Histologically confirmed squamous carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix; (3)Patients with 2018 FIGO stage IIIC2 cervical cancer; (4)At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1; (5)Eastern Cooperative Oncology Group score 0-1; (6)No metastatic diseases; (7)Must have an average life expectancy of 6 months; (8)Participants must have normal organ and marrow function as defined below: (hemoglobin ≥90g/L,neutrophils ≥1.5×109/L, platelets ≥80×109/L, ALB≥30g/L, Total bilirubin≤1.5 x institutional upper limit of normal, AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, Creatinine clearance≥60 mL/min; (9)Patients with menopause, or patients of reproductive potential were required to take effective contraceptive measures for the duration of the study and had a negative pregnancy test result, non-lactating women; (10)Patients volunteered to participate in the study and sign the informed consent. Exclusion criteria: Diagnosed with any other cancer within the past 5 years; Known allergy to any component of the drug; Congenital or acquired immune deficiency (such as 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.); Medical history of vitiligo; asthma which requires bronchodilators for medical intervention; Active infection requiring systemic treatment; Previously treatment with PD-1 and/or PD-L1, or CTLA-4 antibody, or other medications targeting immunomodulatory receptors; Patients with grade>2 unrelieved toxic reactions (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0) caused by any previous treatment; With a history of myocardial infarction,stroke, unstable angina, decompensated heart failure, or deep vein thrombosis; Long-term uncured wounds or fractures; Major surgery or severe traumatic injury, fracture or ulcer within 4 weeks; Pregnant or lactating women; With metastatic diseases; Liver/renal insufficiency; Those who have a history of psychotropic drug abuse and cannot get rid of it or those with mental disorders; Those who have participated in clinical trials with other drugs within 4 weeks; Patients with concomitant diseases or abnormal test results which interfere with the ability to receive anticancer therapy judged by the investigator; Patients could not gain the maximum benefit from this study judged by the investigator.

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

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized (1:1) to Arm A or Arm B.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tislelizumab<br>The external radiation is administered at 45-50Gy/25f and brachytherapy is performed sequentially at 6Gy/time to a total doses of 30 Gy. The concomitant chemotherapy regimen is cisplatin 40mg/m2 on day 1 once every week for 5 weeks. In addition, patients also receive tislelizumab (200 mg, day 1) once every 3 weeks until disease progression or intolerable toxicity occurs or one year. | Drug: tislelizumab<br>* standard radiotherapy with concomitant cisplatin 40mg/m2 once every week for 5 weeks, combined with tislelizumab (200 mg, day 1) once every 3 weeks until disease progression or intolerable toxicity occurs or one year.<br>* Other names: pd-1 antibody;|
| Active Comparator: concurrent chemoradiotherapy<br>The external radiation is administered at 45-50Gy/25f and brachytherapy is performed sequentially at 6Gy/time to a total doses of 30 Gy. The concomitant chemotherapy regimen is cisplatin 40mg/m2 on day 1 once every week for 5 weeks. | Other: concurrent chemoradiotherapy<br>* standard radiotherapy with concomitant cisplatin 40mg/m2 on day 1 once every week for 5 weeks.<br>* Other names: DDP combined with radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year progress free survival rate | Progression-free survival (PFS) is defined as the time between entry into the study and progression of the tumor (in any respect) or death (from any cause). | up to 3 years | 
| side effect rate | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate(ORR) | ORR is defined as the proportion of patients with CR or PR, assessed by RECIST v1.1 per independent central radiologic review. | 3 months, after chemoradiotherapy | 
| 3-year overall survival rate | overall survival rate（OS）is calculated from the date of entry into the study to the date of death or the last follow-up visit. | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical carcinoma, PD-1, chemoradiotherapy