Fluzoparib and Camrelizumab in Treating Patients With R/M NPC That Progressed After First-line Chemotherapy

Study Overview
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Brief Summary
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The aim of this study is to define the efficacy and safety of Fluzoparib and Camrelizumab in treating patients with recurrent/metastatic nasopharyngeal carcinoma that progressed after first-line chemotherapy.

Detailed Description
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Currently, the standard first-line treatment for recurrent/metastatic nasopharyngeal carcinoma is cisplatin-based chemotherapy. The recommended subsequent line therapy is single-agent chemotherapy or single-agent PD-1 antibody (nivolumab or pembrolizumab), according to NCCN guidelines (head and neck cancer, version 2021.3). However, the efficacy of nivolumab or pembrolizumab in subsequent line setting is limited, range from 20-30%. In order to improve the efficacy, we launch this study to evaluate whether combination treatment of PARP inhibitor (Fluzoparib) and PD-1 antibody (Camrelizumab) has the potential to increase efficacy in the subsequent line treatment, meanwhile has tolerable adverse effect.

Official Title
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A Phase II Single-site the Study of the Efficacy and Safety of Fluzoparib and Camrelizumab in Treating Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma That Progressed After First-line Chemotherapy

Conditions
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Nasopharyngeal Carcinoma, Nasopharyngeal Cancer

Intervention / Treatment
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* Drug: Fluzoparib and Camrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign an informed consent; Age older than 18 years old and younger than 75 years old; Patients with histologically confirmed recurrent/metastatic nasopharyngeal carcinoma, that progressed after at least first-line chemotherapy, according to RECIST 1.1 criteria; No previous treatment of PD-1/L1 inhibitors, CTLA-4 inhibitors, other checkpoint inhibitors or immune modulation therapy, or PARP inhibitors; At least one lesion that fulfills the criteria of Evaluable Disease per RECIST 1.1 Criteria; Anticipated overall survival more than 3 months; Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-2; Normal organ function; HBV DNA<500 IU/mL（or 2500 copies/mL）and HCV RNA negative ; Male and no pregnant female, able to adapt birth control methods during treatment. Exclusion Criteria: Hypersensitivity to Fluzoparib or Camrelizumab; Symptomatic spinal cord compression, or high-risk to develop pathological fracture that requires urgent surgery or radiation; Necrotic disease, high-risk of massive bleeding; Suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years; Severe, uncontrolled heart disease, such as more than NYHA II heart failure, unstable angina pectoris, myocardial infarction within 1 year prior to signing inform consent, severe arrhythmia that requires urgent intervention; Previous treatment of PD-1/L1 inhibitors, CTLA-4 inhibitors, other checkpoint inhibitors or immune modulation therapy, or PARP inhibitors; Receive vaccine or live vaccine within 28 days prior to signing the informed consent; Still suffered from adverse effect (more than CTCAE grade 1), that results from previous treatment; Severe, uncontrolled infections within 28 days prior to signing inform consent; Active, known or suspected autoimmune disease; Type I Diabetes, hypothyroidism those only need hormone replacement therapy, vitiligo or inactive asthma who don't need systemic therapy can recruit; HIV positive; Diagnosed as active pulmonary tuberculosis within one year before signing inform consent; or diagnosed as active pulmonary tuberculosis more than one year, but did not receive standardized anti-tuberculosis treatment; Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥500IU/ml, or 2500cps/ml; Positive HCV RNA; History of drug abuse, drug taking, alcohol abuse; Other diseases which may influence the safety or compliance of the clinical trial, such as mental illness, or their family and society factors; Women of child-bearing potential who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination of Fluzoparib and Camrelizumab<br>Fluzoparib,150mg bid po, d1-21, q3w Camrelizumab 200mg iv, d1, q3w | Drug: Fluzoparib and Camrelizumab<br>* Maintenance therapy of Fluzoparib and Camrelizumab, until disease progression or intolerable adverse effect.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Overall response rate, evaluated by independent radiology review board, according to RECIST 1.1 Criteria | Within 2 year post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate | Disease control rate, evaluated by independent radiology review board, according to RECIST 1.1 Criteria | Within 2 year post-treatment | 
| Duration of response | Duration of response, evaluated by independent radiology review board, according to RECIST 1.1 Criteria | Within 2 year post-treatment | 
| Progression-free survival rate at 6 month post-treatment | Progression-free survival rate at 6 month post-treatment | 6 month post-treatment | 
| Overall survival rate at 6 month post-treatment | Overall survival rate at 6 month post-treatment | 6 month post-treatment | 
| Progression-free survival rate at 12 month post-treatment | Progression-free survival rate at 12 month post-treatment | 12 month post-treatment | 
| Overall survival rate at 12 month post-treatment | Overall survival rate at 12 month post-treatment | 12 month post-treatment | 
| Median progression-free survival | Median progression-free survival | Within 2 year post-treatment | 
| Median overall survival | Median overall survival | Within 2 year post-treatment | 
| Adverse effect | Adverse effect, according to CTCAE 4.0.03 criteria | Within 2 year post-treatment | 
| Overall response rate by different PD-L1 TPS subgroups | Overall response rate by different PD-L1 TPS subgroups (≥1% vs. <1%; ≥20% vs. <20%; ≥50% vs. <50%）) | Within 2 year post-treatment | 
| Overall response rate by different homologous recombination repair status (HRR) | Overall response rate by different homologous recombination repair status(germline BRCA mutation/wildtype, HRD positive/negative, germline HRR genes mutations status) | Within 2 year post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP inhibitor, Fluzoparib, checkpoint inhibitor, PD-1 inhibitor, Camrelizumab