An Open-label, Single-arm, Phase II Study to Investigate the Efficacy and Safety of Niraparib Combined With Anlotinib Maintenance Retreatment in PSR Ovarian Cancer Patients, Who Have Previously Received PARPi Maintenance Treatment.

Peking Union Medical College Hospital0 sites35 target enrollmentJune 2022

ConditionsEpithelial Ovarian Cancer

InterventionsNiraparib

DrugsNiraparib

Overview

Phase: Phase 2
Intervention: Niraparib
Conditions: Epithelial Ovarian Cancer
Sponsor: Peking Union Medical College Hospital
Enrollment: 35
Primary Endpoint: Progression free survival (PFS)
Status: Not yet recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This study will be an open-label, single-arm, prospective, exploratory phase II trial to investigate the efficacy and safety of niraparib maintenance retreatment in platinum- sensitive recurrent (PSR) epithelial ovarian cancer (EOC) patients (including patients with primary peritoneal and/or fallopian tube cancer).

Detailed Description

This study will investigate the efficacy and safety of niraparib maintenance re-treatment in patients with PSR non-mucinous EOC, who have previously received maintenance therapy with a Polyadenosine 5'diphosphoribose \[poly (ADP ribose)\] polymerisation inhibitor (PARPi) and a complete or partial radiological response to subsequent treatment with platinum-based chemotherapy or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy). Patients will be enrolled, given niraparib and anlotinib maintenance treatment until disease progression or untolerated toxicity.

Registry

clinicaltrials.gov

Start Date

June 2022

End Date

September 2024

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Peking Union Medical College Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of informed consent prior to any study specific procedures.
•Female patients ≥18 years of age, with histologically diagnosed platinum sensitive recurrent high-grade serous or endometrioid epithelial ovarian cancer (EOC) (including primary peritoneal and/or fallopian tube cancer).
•BRCA mutation status is known.
•Patients must have received one prior PARPi therapy, PARPi therapy includes any agent (including niraparib) used in a maintenance setting and the duration of maintenance treatment ≥6 months.
•Patients had received ≤3 lines of chemotherapy, the time between the penultimate line of platinum-containing chemotherapy and the last platinum-containing chemotherapy was \> 6 months. For example, if a patient receives a non-platinum type of chemotherapy between the penultimate line of platinum-containing chemotherapy and the last platinum-containing chemotherapy, patient will be eligible if all the eligibility criteria are met.
•The most recent round of platinum-containing chemotherapy should have included ≥4 cycles of treatment , in the opinion of the investigator, in response (partial or complete radiological response) or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy) .
•Patients must have either CA-125 in the normal range or CA-125 decrease by more than 90% during last line chemotherapy and that is stable for at least 7 days (ie, no increase \> 15% from nadir).
•Patients can have received bevacizumab during this course of treatment. Bevacizumab use as part of an earlier line of therapy is permitted.
•Patients must be enrolled within 8 weeks of their last dose of chemotherapy (last dose is the day of the last infusion).
•Patients must have a life expectancy ≥4 months.

Exclusion Criteria

•Allergy to active or inactive ingredients of niraparib or drugs with similar chemical structures.
•Allergy to active or inactive ingredients of anlotinib or drugs with similar chemical structures.
•Active and uncontrollable brain metastasis or leptomeningeal metastasis. Patients with spinal cord compression can still be considered if they have received targeted treatment and have evidence of clinical stability of the disease for at least \> 28 days (controlled brain metastasis must have received radiotherapy or chemotherapy at least 1 month prior to study entry; patients may not have new symptoms related to brain lesions or symptoms indicating disease progression and either take stable dose of hormone or do not need to take hormone).
•Major surgery performed within 3 weeks before enrollment, or any surgical effects that have not recovered from the surgery, or chemotherapy.
•Palliative radiotherapy encompassing \>20% of the bone marrow within 1 week of the first dose of study treatment.
•Any other malignant tumor exclude ovarian cancer has been diagnosed within 2 years before enrollment (except for completely treated basal or squamous cell skin cancer).
•Current or previous myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
•Other severe or uncontrolled diseases, including but not limited to: Uncontrollable nausea and vomiting, inability to swallow study drug, and any gastrointestinal disease that may interfere with the absorption and metabolism of the drug; Active viral infections, such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus and so on; Uncontrolled epileptic seizures, unstable spinal cord compression, superior vena cava syndrome or other psychiatric disorders that may affect patients' informed consent; Immunodeficiency (except for splenectomy), or other diseases that investigators believe may expose patients to high-risk toxicity.
•Have the risk or tendency of bleeding and history of thrombosis: CTCAE grade 2 bleeding event occurred within 3 months prior to screening or CTCAE ≥ grade 3 bleeding event occurred within 3 months prior to screening;
•Have history of gastrointestinal bleeding or confirmed bleeding tendency within 6 months prior to screening. e.g. esophageal varices with bleeding risk, local active ulcer focus or fecal occult blood above ++.

Arms & Interventions

Niraparib combined with Anlotinib

Participants received Niraparib 200mg or 300mg QD PO continually and Anlotinib 10mg QD PO on Days 1-14 (21 days/cycle) .

Intervention: Niraparib

Outcomes

Primary Outcomes

Progression free survival (PFS)

Time Frame: Up to 1 year

PFS is assessed as the time from niraparib treatment initiation to the earlier date of assessment of progression, as assessed by RECIST v1.1 criteria based on Investigator assessment, or death by any cause in the absence of progression

Secondary Outcomes

Time to First Subsequent Therapy (TFST)(The date of initiation of niraparib treatment in the current study to the start date of the first subsequent anticancer therapy assessed up to 15 months.)
Overall Survival (OS)(From the time of enrollment to date of death by any cause assessed up to 36 months.)
Frequency and severity of adverse effects as defined by CTCAE version 5.0(From the time of enrollment to date of 30 days after the last study drug administration.)
Progression Free Survival (PFS) Rate at 6 months(6 months)