Toripalimab Combined With Concurrent Chemoradiotherapy in Cervical Cancer

Study Overview
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Brief Summary
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To explore the efficacy and tolerance of adding toripalimab simultaneously and subsequently to concurrent platinum-based chemoradiotherapy in patients with locally advanced cervical cancer.

Detailed Description
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Up to now, there have been several prospective studies exploring the effectiveness of PD-1 inhibitors in patients with recurrent/ metastatic cervical cancer. The results showed that the overall objective response rate (ORR) was between 12.2% and 55.6%, and pembrolizumab was approved by the US Food and Drug Administration for patients with advanced PD-L1-positive cervical cancer who experienced progression during or after chemotherapy. However, the evidence of using PD-1 inhibitors together with concurrent chemotheradiotherapy in patients with locally advanced cervical cancer is rare, so we initiated this single arm prospective phase II clinical study. The purpose is to explore the efficacy and tolerance of adding toripalimab simultaneously and subsequently to concurrent chemoradiotherapy in patients with locally advanced cervical cancer.

Official Title
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Toripalimab Combined With Concurrent Platinum-based Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: An Open-Label, Single-Arm, Phase II Trial

Conditions
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Cervical Cancer

Intervention / Treatment
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* Combination Product: Toripalimab Combined With Concurrent Platinum-based Chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 75; Untreated patients with pathologically proven locally advanced cervical cancer; Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 Adequate hematological, renal and hepatic functions: Hemoglobin > 8.0 g/dl Neutrophils > 2000 cells/μl; Leukocytes > 4 × 109/L Platelets > 100 × 109/L g. Serum urea nitrogen (BUN) ≤ 1.5 × upper normal limit (UNL) h. Serum creatinine (Cr) ≤ 1.5 × upper normal limit (UNL) d. Serum ALT/AST ≤ 2.5× UNL e. Serum Total bilirubin ≤ 1.5× UNL Life expectancy > 6 months Eligible for concurrent chemoradiotherapy assessed by principle investigator; No obvious active bleeding; Written informed consent must be available before study registration Exclusion Criteria: Recurrent or distant metastatic disease; Prior malignancies (other than curable non-melanoma skin cancer) within 5 years; Active autoimmune diseases requiring systemic treatment or other diseases requiring long-term use of substantial amount of hormones or other immunosuppressants; Patients who need to receive systemic corticosteroids (dose equivalent to or higher than prednisone 10mg qd) or other immunosuppressants within 14 days before enrollment or during the study; Vaccination of live attenuated vaccine 30 days before enrollment, or planned vaccination of live attenuated vaccine during the study; Previous organ transplantation or HIV patients; Allergic to macromolecular proteins /monoclonal antibodies, or to any test drug component; Active acute or chronic viral hepatitis B or C. Hepatitis B virus (HBV) DNA> 2000IU/ml or 104 copies/ml; hepatitis C virus (HCV) RNA> 103 copies/ml.

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: PD-1 arm<br>PD-1 concurrent with and subsequent after concurrent chemoradiotherapy | Combination Product: Toripalimab Combined With Concurrent Platinum-based Chemoradiotherapy<br>* Toripalimab 240mg intravenously(IV) every 3 weeks (Q3W) concurrent with chemoradiotherapy; 6 cycles of Toripalimab 240mg intravenously(IV) every 3 weeks (Q3W) after chemoradiotherapy; Toripalimab 240mg intravenously(IV) every 6 weeks (Q6W) thereafter until the whole treatment period reached one year since the beginning.<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 | 

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 | 2 years | 
| Overall survival | Time from diagnosis of disease of treatment until death due to any cause | 3 years |