A Phase 2 Trial of Fluzoparib Combined With Apatinib Versus Fluzoparib Monotherapy in Treatment With Relapsed Ovarian Cancer Patients

Study Overview
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Brief Summary
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This is a multicenter, randomized, open-label, 2-arm Phase 2 study to evaluate the efficacy and safety of Fluzoparib with Apatinib versus Fluzoparib alone, as treatment, in relapsed ovarian cancer patients. The study contains a Safety Lead-in Phase in which the safety and tolerability of Fluzoparib+Apatinib will be assessed prior to the Phase 2 portion of the study.

Official Title
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A Phase 2 Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Fluzoparib Combined With Apatinib Versus Fluzoparib Monotherapy in the Treatment of Relapsed Ovarian Cancer Patients

Conditions
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Relapsed Ovarian Cancer

Intervention / Treatment
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* Drug: Fluzoparib+Apatinib
* Drug: Fluzoparib
* Drug: Fluzoparib+Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically diagnosed high-grade serous or endometrioid recurrent ovarian,fallopian tube,or peritoneal cancer. Patients must have received at least 2 previous platinum-containing regimens. At least one target lesion. ECOG performance status 0-1. Adequate bone marrow, kidney and liver function. Exclusion Criteria: Prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor or Apatinib.For exploratory cohort ，patients who received PARP inhibitor are eligible; Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix allowed; Radiation or anti-hormonal therapy or anticancer therapy within 14 days before first administration; Known to be human immunodeficiency virus positive; Known active hepatitis C virus, or known active hepatitis B virus; Untreated and/or uncontrolled brain metastases; Patients with clinical symptoms of cancer ascites, pleural effusion, who need to drainage, or who have undergone ascites drainage within 3 months prior to the first administration; Pregnant or breast-feeding women.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety Lead-in or Parallel， Fluzoparib+Apatinib<br>Participants will receive Fluzoparib-Apatinib combination until progression | Drug: Fluzoparib+Apatinib<br>* Fluzoparib-Apatinib combination<br>|
| Active Comparator: Fluzoparib monotherapy<br>Participants will receive Fluzoparib monotherapy until progression | Drug: Fluzoparib<br>* Fluzoparib monotherapy<br>|
| Other: Exploratory cohort: Fluzoparib+Apatinib<br>Participants who has previously received PARP inhibitor, will receive Fluzoparib-Apatinib combination until progression | Drug: Fluzoparib+Apatinib<br>* Fluzoparib-Apatinib combination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Safety Lead-in) dose limited toxicity (DLT) of Fluzoparib+Apatinib in the first cycle |  | up to 28 days | 
| (Safety Lead-in) Recommended Phase II Dose (RP2D) of Fluzoparib+Apatinib |  | up to 28 days | 
| (Phase 2) Objective response rate（ORR） in relapsed ovarian cancer patients | Defined as Objective response rate per RECIST 1.1 criteria according to Investigator's assessment | Assessed up to a maximum of 20 months | 
| (Exploratory research) Objective response rate（ORR） in relapsed ovarian cancer patients | Defined as Objective response rate per RECIST 1.1 criteria according to Investigator's assessment | Assessed up to a maximum of 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs+SAEs | Adverse Events and Serious Adverse Events | from the first drug administration to within 30 days for the last treatment dose | 
| Progression free survival (PFS) | Defined as Progression free survival per RECIST 1.1 criteria according to Investigator's assessment | up to 20 months | 
| Disease control rate (DCR) | Complete response + Partial response + Stable disease (CR+PR+SD) based on RECIST 1.1 | up to 20 months | 
| Duration of response (DoR) | Time from documentation of tumor response to disease progression assessed among patients who had an objective response | up to 20 months | 
| Response rate by RECIST 1.1 criteria |  | up to 20 months | 
| Response rate by GCIG CA125 |  | up to 20 months |