A Trial of Maintenance Treatment With Fluzoparib Versus Placebo in Relapsed Ovarian Cancer Patients

NCT03863860CompletedPHASE3INTERVENTIONAL

Summary

Key Facts

Lead Sponsor

Jiangsu HengRui Medicine Co., Ltd.

Enrollment

252

Start Date

2019-04-30

Completion Date

2022-01-10

Study Type

INTERVENTIONAL

Official Title

A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Trial of Maintenance Treatment With Fluzoparib Capsules Versus Placebo in Patients With Platinum-sensitive Recurrent Ovarian Cancer

Interventions

Fluzoparib capsulesPlacebo capsules

Conditions

Ovarian Cancer

Eligibility

Age Range

18 Years+

Sex

FEMALE

Inclusion Criteria:

1. Histologically diagnosed high-grade serous or endometrioid ovarian cancer (including primary peritoneal and fallopian tube cancer)
2. Completion of ≥2 previous platinum-containing regimens
3. Complete response (CR) or partial response (PR) achieved with last platinum-based chemotherapy regimen as determined by investigator
4. Ability to be randomized ≤8 weeks after last dose of platinum

Exclusion Criteria:

1. Prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor
2. Patients who have received other study drug treatment within 4 weeks prior to the first administration(\< 5 elimination half-lives of the study drug molecular targeted anti-cancer drugs).
3. Patients with clinical symptoms of cancer ascites, pleural effusion, who need to drainage, or who have undergone ascites drainage within 2 months prior to the first administration.

Outcome Measures

Primary Outcomes

Progression free survival(PFS) by Blinded Independent Review Committee (BIRC) in relapsed ovarian cancer patients

Defined as progression free survival per RECIST 1.1 criteria

Time frame: up to 2 years

Progression free survival(PFS) by BIRC in relapsed ovarian cancer patients with Breast cancer susceptibility gene(BRCA) mutant

Defined as progression free survival per RECIST 1.1 criteria

Time frame: up to 2 years

Secondary Outcomes

Progression free survival(PFS) in relapsed ovarian cancer patients

PFS is Progression-Free-Survival per RECIST 1.1 criteria

Time frame: up to 2 years

Time to progression(TTP) by Gynecological Cancer Intergroup(GCIG) CA 125 criteria

TTP is Time to Progression

Time frame: up to 2 years

Chemotherapy free interval (CFI) CFI

CFI is the time from last platinum dose until initiation of next anticancer therapy (excluding maintenance therapy if used following the penultimate regimen)

Time frame: up to 2 years

overall survival(OS)

OS is the time interval from the start of treatment to death due to any reason or lost of follow-up

Time frame: up to 3 years

Objective Response Rate

Objective Response Rate complete or partial response per RECIST 1.1 criteria

Time frame: At baseline,at the time point of every 12 weeks, up to 2 years

Adverse Events(AEs) and Serious Adverse Events (SAEs)

assess the safety and tolerability of Fluzoparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients by record the number of Participants with of AEs and SAEs, and the proportion of patients with AEs and SAEs, etc.

Time frame: from the first drug administration to within 30 days for the last treatment dose

Locations

Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China

Linked Papers

2022-04-11

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial

PURPOSE This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P &lt; .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

A Trial of Maintenance Treatment With Fluzoparib Versus Placebo in Relapsed Ovarian Cancer Patients