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

Phase 2

Recruiting

• Conditions: Nasopharyngeal Carcinoma; Nasopharyngeal Cancer
• Interventions: Drug: Fluzoparib and Camrelizumab

• Registration Number: NCT04978012
• Lead Sponsor: Fudan University

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-07-25
• Study First Submitted: 2021-07-25
• Study First Submitted QC: 2021-07-25
• Study First Posted: 2021-07-27
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-04
• Last Update Posted: 2022-06-07
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Sign an informed consent;
2. Age older than 18 years old and younger than 75 years old;
3. Patients with histologically confirmed recurrent/metastatic nasopharyngeal carcinoma, that progressed after at least first-line chemotherapy, according to RECIST 1.1 criteria;
4. No previous treatment of PD-1/L1 inhibitors, CTLA-4 inhibitors, other checkpoint inhibitors or immune modulation therapy, or PARP inhibitors;
5. At least one lesion that fulfills the criteria of "Evaluable Disease" per RECIST 1.1 Criteria;
6. Anticipated overall survival more than 3 months;
7. Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-2;
8. Normal organ function;
9. HBV DNA<500 IU/mL（or 2500 copies/mL）and HCV RNA negative ;
10. Male and no pregnant female, able to adapt birth control methods during treatment.

Exclusion Criteria

1. Hypersensitivity to Fluzoparib or Camrelizumab;
2. Symptomatic spinal cord compression, or high-risk to develop pathological fracture that requires urgent surgery or radiation;
3. Necrotic disease, high-risk of massive bleeding;
4. Suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years;
5. 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;
6. Previous treatment of PD-1/L1 inhibitors, CTLA-4 inhibitors, other checkpoint inhibitors or immune modulation therapy, or PARP inhibitors;
7. Receive vaccine or live vaccine within 28 days prior to signing the informed consent;
8. Still suffered from adverse effect (more than CTCAE grade 1), that results from previous treatment;
9. Severe, uncontrolled infections within 28 days prior to signing inform consent;
10. 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;
11. HIV positive;
12. 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;
13. Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥500IU/ml, or 2500cps/ml; Positive HCV RNA;
14. History of drug abuse, drug taking, alcohol abuse;
15. Other diseases which may influence the safety or compliance of the clinical trial, such as mental illness, or their family and society factors;
16. Women of child-bearing potential who are pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of Fluzoparib and Camrelizumab	Fluzoparib and Camrelizumab	Fluzoparib,150mg bid po, d1-21, q3w Camrelizumab 200mg iv, d1, q3w

Primary Outcome Measures

Name	Time	Method
Overall response rate	Within 2 year post-treatment	Overall response rate, evaluated by independent radiology review board, according to RECIST 1.1 Criteria

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Fudan Universtiy Shanghai Cancer Centre; 🇨🇳 Shanghai, Shanghai, China