Induction Toripalimab and Chemotherapy in Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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To explore the efficacy of incorporating neoadjuvant immunotherapy into neoadjuvant chemotherapy in locally advanced cervical cancer patients with high risk of recurrence.

Detailed Description
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For locally advanced cervical cancer patients undergoing definitive chemoradiotherapy, distant metastasis has become a major concern. In this study, investigators selected a subgroup of patients with theoretically higher risk of distant metastasis and intensified their systematic treatment by incorporating PD-L1 inhibitors into neoadjuvant chemotherapy, in order to reduce their risk of distant metastasis and achieve good disease-free survival.

Official Title
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Induction Toripalimab and Chemotherapy in Locally Advanced Cervical Cancer Patients With High Risk of Recurrence: A Prospective, Single-Arm, Phase II Trial

Conditions
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Cervical Cancer, Induction Chemotherapy, Immunotherapy

Intervention / Treatment
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* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated locally advanced cervical cancer patients with clear pathological diagnosis 2019 FIGO stage IIIB-IVA. For patients with stage IIIC disease, the short diameter of their metastatic lymph nodes should ≥1.5cm Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Life expectancy > 6 months Able to tolerate concurrent chemoradiotherapy assessed by researches No obvious active bleeding; Adequate hematological, renal and hepatic functions: No concomitant malignancies Female subjects of childbearing potential should have a negative pregnancy test and must take effective and reliable contraceptive measures during the clinical trial period; Voluntarily-signed informed consent. Exclusion Criteria: Concomitant other malignancies; Patients with metastatic or recurrent disease; Patients received any form of treatment before enrollment; Severe concomitant chronic diseases (diabetes, hypertension, etc.) or acute infections; Impaired hematological, renal or hepatic functions: Hemoglobin < 9.0 g/dl Neutrophils < 2000 cells/μl; Leukocytes < 4 × 109/L Platelets > 100 × 109/L Serum ALT/AST > 2.5×UNL Serum Total bilirubin > 1.5× UNL g. Serum urea nitrogen (BUN) > 1.5 × upper normal limit (UNL) h. Serum creatinine (Cr) > 1.5 × upper normal limit (UNL) Patients with obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency or severe heart valve disease; Patients with uncontrolled mental diseases; Pregnant or lactating woman; Participating in other clinical trials; Anyone considered not suitable for enrollment by principal investigator;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction immunotherapy and chemotherapy<br>Patients enrolled in this arm would receive neoadjuvant immunotherapy and chemotherapy before definitive chemoradiation | Drug: Toripalimab<br>* Patients enrolled in this arm would receive three cycles of induction treatment before receiving definitive chemoradiotherapy. The specific regimen is: Paclitaxel(135mg/m2,ivd, d1)+cisplatin(75mg/m2,ivd,d1-3)+Toripalimab (240mg,ivd,d1)±bevacizumab(ivd, d1)/q21d. Patients would receive pelvic MRI to evaluate the regression status of tumor after three cycles of induction treatment. Patients with satisfying tumor regression would receive definitive chemoradiotherapy afterwards. During chemoradiotherapy, patients would receive weekly cisplatin (40mg/m2) and 240mg toripalimab every three weeks. After chemoradiotherapy, patients would receive another three cycles of consolidated treatment (regimen identical to induction treatment).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) using RECIST v1.1 | 1 year | 
| Volume changes of core radiation targets and irradiated normal tissues after induction treatment | Volume change of PTV, PGTVnd, Bladder V45, V50, Dmax, Dmean, Rectum V45, V50, Dmax, Dmean, Bowel bag V45, V50 | 5-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Time from diagnosis of disease to disease progression or death due to any cause | 1-year, 2-year | 
| Distant metastasis-free survival | Time from diagnosis to distant metastasis or death due to any cause | 1-year, 2-year | 
| Incidence of treatment-related side effects | Incidence of treatment-related side effects (i.e., radiation-related proctitis, cystitis, ,vaginitis, etc.) | 5-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, immunotherapy, neoadjuvant chemotherapy, chemoradiation