Pd-1 Antibody Combined Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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Cervical cancer is one of the major health problems for chinese women. Besides surgery and radiotherapy, neoadjuvant chemotherapy has been proved to be an effective program by many studies. However, not all patients respond well to neoadjuvant chemotherapy. This is an open-label, single-arm, multi-center clinical trial to evaluate whether PD-1 in combination with neoadjuvant chemotherapy will achieve better objective response rate.

Detailed Description
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Subjects will receive therapy Q3W until evaluation of efficacy. The first cycle include cisplatin and albumin-bound paclitaxel. A combination of anti-PD-1 antibody (SHR-1210) with cisplatin and albumin-bound paclitaxel would be given in second and third cycles. Patients who have demonstrated complete or partial tumour responses （CR/PR）will receive surgery and receive postoperative adjuvant therapy in accordance with NCCN guideline. Patients who have demonstrated stable disease or progressive disease （SD/PD）will receive concurrent radiochemotherapy.

Official Title
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Study of Pd-1 Antibody in Combination With Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer

Conditions
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Uterine Cervical Neoplasm, Uterine Cervical Cancer, Cervical Cancer

Intervention / Treatment
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* Drug: Cisplatin+Albumin-bound paclitaxel (1 cycle) and PD-1 monoclonal antibody+Cisplatin+Albumin-bound paclitaxel (2 cycles)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced (2019 FIGO staged IB3, IIA2 and IIB/IIIC1r（tumor size> 4cm) ) cervical cancer and had not received any treatment before. Histologically confirmed squamous carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix. Pathological examination of the PD-L1 positive（Combined score Positive Score≥1）. Females 18-65 years of age. Eastern Cooperative Oncology Group score 0-1. WBC≥3.5*10^9/L, NEU≥1.5*10^9/L, Platelet≥80×10^9 /L; AST and ALT ≤1.5 times normal upper limit; Total bilirubin ≤1.5 times the upper limit of normal value; serum creatinine and blood urea nitrogen ≤the upper limit of normal value. Well-compliance and willing to keep in touch. Willing to participate in this study, and sign the informed consent. Exclusion Criteria: Active or known or suspected autoimmune disease requires a system treatment as follows but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, asthma requiring intervention with bronchodilators. HIV infection, active HBV/HCV. Condition requiring systemic treatment with small doses of corticosteroids within 1 months or large doses of corticosteroids within 3 months prior to randomization. Any primary malignancy within 5 years. Participate in other drug clinical trials at the same time. Pregnant or lactating female patients. Comorbidity including but not limited to: heart diseases (grade III-IV cardiac insufficiency (NYHA standard); central nervous system diseases or nonfunctional behavior; hematological system diseases; liver or kidney malformation or history of surgery. Drug or alcohol abuse. Unable or unwilling to sign informed consents. Not eligible for the study judged by researchers.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Patients receive 1 cycle of cisplatin and albumin-bound paclitaxel combined neoadjuvant chemotherapy and subsequent 2 cycles of PD-1 antibody combined neoadjuvant chemotherapy. | Drug: Cisplatin+Albumin-bound paclitaxel (1 cycle) and PD-1 monoclonal antibody+Cisplatin+Albumin-bound paclitaxel (2 cycles)<br>* PD-1 monoclonal antibody （SHR-1210)：200mg，IV infusion，Q3W Cisplatin：75-80 mg/m2, IV infusion, Q3W Albumin-bound paclitaxel: 260 mg/m2，30min，IV infusion, Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of the participants in the ITT population who have a Complete Response or Partial Response. The ORR will be assessed by a blind independent central reviewer per RECIST 1.1 | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | Pathological response rate is defined as the percentage of the participants in the ITT population who have complete pathologic remission or the infiltration depth of cervical lesions was < 3mm in histological examination. | 3 months | 
| Event-free survival (EFS) | EFS defined as the time interval from the date of randomization to disease progression, local or distant recurrence (in patients undergoing surgery), or death due to any cause. | 5 years | 
| Overall survival （OS） | OS is defined as the time from the date of randomization until death. | 5 years |