NCT03075462

Brief Summary

Fluzoparib is an oral potent, selective poly-ADP ribose polymerase-1 (PARP-1) and PARP-2 inhibitor; Apatinib is an oral selective vascular endothelial growth factor receptor (VEGFR) inhibitor. This open-label, dose finding phase I trial studies the tolerability and the best dose of fluzoparib in combination with apatinib and to see how well these two drugs work together in the treatment of patients with recurrent ovarian cancer or triple negative breast cancer. The safety and efficacy of fluzoparib in combination with apatinib will be explored. Both dose escalation and dose expansion parts are included in this study.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
98

participants targeted

Target at P75+ for phase_1 ovarian-cancer

Timeline
Completed

Started Mar 2017

Typical duration for phase_1 ovarian-cancer

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 6, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 9, 2017

Completed
Same day until next milestone

Study Start

First participant enrolled

March 9, 2017

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 22, 2021

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 13, 2021

Completed
Last Updated

July 1, 2022

Status Verified

June 1, 2022

Enrollment Period

4.5 years

First QC Date

March 6, 2017

Last Update Submit

June 30, 2022

Conditions

Ovarian CancerTriple Negative Breast Cancer

Keywords

PARP inhibitorVEGFR inhibitorCombination therapyOvarian CancerTriple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

  • The type and incidence of adverse events [safety and tolerability]

    Adverse events defined according to Common Terminology for Adverse Events (CTCAE) v4.03

    From screening up to 28 days after end of treatment

Secondary Outcomes (9)

  • Objective Response Rate (ORR)

    24 months (approx) from the start of treatment

  • Disease Control Rate (DOR)

    24 months (approx) from the start of treatment

  • Time to Progression (TTP)

    From date of enrollment until the date of first objective progression or CA-125 progression (only for ovarian cancer patients), assessed up to 36 months

  • Overall Survival (OS)

    From Cycle 1, Day 1 until death or up to 48 months (approx)

  • Cmax

    From the start of fluzoparib treatment alone to Cycle 2, Day 1 of combined treatment

  • +4 more secondary outcomes

Study Arms (1)

Fluzoparib + Apatinib

EXPERIMENTAL

Fluzoparib and apatinib will be separately administered to patients on the 1st and 4th day, respectively. Then from the 7th day they are administered continuously and orally in combination, 28 days per cycle, until disease progression or unacceptable toxicity.

Drug: FluzoparibDrug: Apatinib

Interventions

FluzoparibDRUG

Fluzoparib either at 40,60,80mg twice daily,capsule oral.

Also known as: SHR3162, HS10160
Fluzoparib + Apatinib
ApatinibDRUG

Apatinib at 250mg once daily, tablet oral

Fluzoparib + Apatinib

Eligibility Criteria

Age18 Years - 70 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Life expectancy of more than 12 weeks.
  • Histologically or cytologically confirmed high-grade papillary-serous epithelial ovarian cancer，primary peritoneal, or fallopian tube cancers; subjects with a known deleterious breast cancer gene (BRCA) mutation and any other high-grade histology are also eligible. Subjects should have platinum-sensitive disease, where platinum-sensitive disease is defined as having had a \> 6 month interval since last receiving platinum therapy prior to disease recurrence. Additionally, subjects with histologically or cytologically confirmed triple negative breast cancer (TNBC）, that is locally advanced or metastatic, are also eligible.
  • Prior therapy：subjects with ovarian cancer，primary peritoneal, or fallopian tube cancers have received only 2 lines of platinum-based chemotherapies, and TNBC patients have received only 1 line of standard chemotherapy. Each prior chemotherapy must be given for at least 2 cycles.
  • At least one measurable lesion that can be accurately assessed by imaging (CT/MRI) at baseline
  • Subjects who have overall good overall general condition.
  • Signed informed consent.

You may not qualify if:

  • Subjects who received any previous treatment with any PARP inhibitors.
  • Subjects who received any previous treatment with any VEGFR inhibitors.
  • Less than 4 weeks from the last clinical trial.
  • Less than 4 weeks from the last radiotherapy, chemotherapy, surgery, hormone treatment and target therapy.
  • Unstable or uncontrolled hypertension.
  • Subjects that are unable to swallow, or dysfunction of gastrointestinal absorption.
  • Subjects with brain metastases.
  • Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.
  • Subjects with a known hypersensitivity to fluzoparib, apatinib or any of the excipients of the products.
  • Ongoing infection (determined by investigator).
  • History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
  • Pregnant or breast-feeding women.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Beijing Cancer Hosptial

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (1)

  • Liu Y, Wang W, Yin R, Zhang Y, Zhang Y, Zhang K, Pan H, Wang K, Lou G, Li G, Zhang R, Li K, Rao J, Zhang B, Wang Y, Wang Q, Gao Y, Li H. A phase 1 trial of fuzuloparib in combination with apatinib for advanced ovarian and triple-negative breast cancer: efficacy, safety, pharmacokinetics and germline BRCA mutation analysis. BMC Med. 2023 Sep 29;21(1):376. doi: 10.1186/s12916-023-03046-8.

    PMID: 37775744DERIVED

MeSH Terms

Conditions

Ovarian NeoplasmsTriple Negative Breast Neoplasms

Interventions

fluzoparibapatinib

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersBreast NeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 6, 2017

First Posted

March 9, 2017

Study Start

March 9, 2017

Primary Completion

August 22, 2021

Study Completion

December 13, 2021

Last Updated

July 1, 2022

Record last verified: 2022-06

Locations

CN(1)