NCT03154281

Evaluation of the Safety and Tolerability of Niraparib With Everolimus in Advanced Gynecologic Malignancies and Breast

A Phase 1 Evaluation of the Safety and Tolerability of Niraparib in Combination With Everolimus in Advanced Gynecologic Malignancies and Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Avera McKennan Hospital & University Health Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Open-label, cohort study to determine the feasibility and tolerability of the combination of daily niraparib and daily or thrice weekly everolimus for one 28-day cycle in patients with advanced ovarian and breast cancer.

Detailed description

The goal of this study is to determine a maximum tolerated dose of the combination of niraparib and everolimus. To do this, investigators will estimate the maximum tolerated dose that is defined as the dose level at which less than one-third of patients will experience a dose-limiting toxicity. A traditional dose escalation design will be used, beginning with the lowest dose level and escalating to the maximum allowable dose level as specified in the protocol. One of the following outcomes will determine the treatment of subsequent patients: * If none of the three patients experiences a dose-limiting toxicity , the next group of patients will be entered in the next higher dose cohort. All patients within a cohort must have completed at least one cycle (28 days) prior to initiation of the next cohort of patients. * If one of the three patients experiences a dose-limiting toxicity , three more patients will be accrued at the current dose level. Subsequently, if only one of the six patients treated at this level experiences a dose-limiting toxicity , the dose will be escalated to the next higher dose in the next group of patients. If two or more of the six patients experiences a dose-limiting toxicity , the maximum tolerated dose has been exceeded and is defined as the previous dose at which no more than 1/3 experienced a dose-limiting toxicity . * If at least two of the three experience a dose-limiting toxicity , the maximum tolerated dose has been exceeded and is defined as the previous dose at which no more than 1/3 experienced a dose-limiting toxicity . If the lowest allowable dose level exceeds the maximum tolerated dose, the study will be terminated and the combination will not be deemed safe for use in this population. Additionally, the highest dose level will not be exceeded, even if no dose-limiting toxicities are experienced at that dose. Investigators will summarize the adverse events overall and by individual adverse event categories. Serious adverse events will be summarized in a similar manner. These summaries will be performed overall and for each dose cohort. Investigators will summarize all events as well as the highest grade for a given subject. Investigators will summarize the number of subjects that exhibit a dose-limiting toxicity at each dose cohort and describe the dose-limiting toxicity for each subject, if applicable.

Conditions

• Breast Cancer
• Ovarian Cancer

Interventions

Type	Name	Description
DRUG	niraparib	Niraparib 100 mg will be administered orally once daily continuously. Niraparib will be administered as a flat-fixed dose (100mg, 200 mg, or 300 mg daily) depending on the cohort the patient is enrolled to, and not by body weight or body surface area. Each dose should be swallowed whole without chewing. The consumption of water is permissible. Patients should take doses at approximately the same times each day, and record this information in the patient diary. Patients will be provided with a diary in which to record their intake of study drug. However, the actual number of doses taken by the patient must be calculated from the number of tablets dispensed and returned.
DRUG	everolimus	Everolimus 5 mg tablets will be used. Everolimus will be self-administered orally on a daily basis and doses will either be 5 mg (1 tablet) thrice weekly or 5 mg daily depending on the cohort the patient is enrolled to. Each cycle will be 28 days; everolimus will be taken continuously with no rest between cycles.

Timeline

• Start date: 2017-07-26
• Primary completion: 2021-04-21
• Completion: 2023-05-01
• First posted: 2017-05-16
• Last updated: 2024-08-01
• Results posted: 2024-08-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study