Trial Outcomes & Findings for Evaluation of the Safety and Tolerability of Niraparib With Everolimus in Advanced Gynecologic Malignancies and Breast (NCT NCT03154281)

Last Updated: 2024-08-01

Results Overview

The DLT criteria for adverse events occurring in Cycle 1 while determining the maximum tolerated dose (MTD) are described in the protocol. The number of patients who experience DLT from the trial treatment is recorded.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

From the start of treatment to 30 days after the first dose of study drug

Results posted on

2024-08-01

Participant Flow

Participants took part in this study at Avera Cancer Institute in Sioux Falls, South Dakota, United States from July 2017 to May 2021.

A total of 14 participants with a gynecologic malignancy or breast cancer (triple negative or hormone receptor positive only) were enrolled in this study.

Participant milestones

Participant milestones
Measure	Cohort 1 (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.
Overall Study STARTED	8	6
Overall Study COMPLETED	7	4
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=8 Participants (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 n=6 Participants (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.	Cohort 3 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 200 mg daily 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. 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.	Cohort 4 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 300 mg daily 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. 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.	Total n=14 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=8 Participants	0 Participants n=6 Participants	—	—	0 Participants n=14 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=8 Participants	4 Participants n=6 Participants	—	—	7 Participants n=14 Participants
Age, Categorical >=65 years	5 Participants n=8 Participants	2 Participants n=6 Participants	—	—	7 Participants n=14 Participants
Age, Continuous	67.5 years n=8 Participants	62 years n=6 Participants	—	—	64.5 years n=14 Participants
Sex: Female, Male Female	8 Participants n=8 Participants	6 Participants n=6 Participants	—	—	14 Participants n=14 Participants
Sex: Female, Male Male	0 Participants n=8 Participants	0 Participants n=6 Participants	—	—	0 Participants n=14 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	8 participants n=8 Participants	6 participants n=6 Participants	—	—	14 participants n=14 Participants

PRIMARY outcome

Timeframe: From the start of treatment to 30 days after the first dose of study drug

Population: No patient was enrolled in Cohort 3 or Cohort 4.

Outcome measures

Outcome measures
Measure	Cohort 1 n=8 Participants (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 n=6 Participants (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.	Cohort 3 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 200 mg daily 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. 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.	Cohort 4 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 300 mg daily 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. 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.
Number of Patients Who Developed Does-limiting Toxicity (DLT)	0 Participants	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From beginning of study to the end of the 2nd cycle, and then at 16 weeks if the patient has stable disease or better.

Population: One out of eight patients in Cohort 1 was not evaluable due to rapid progression in cycle 1. One out of six patients in Cohort 2 was not evaluable due to DLT and treatment was discontinued in cycle 1. No patients was enrolled in Cohort 3 or Cohort 4.

Tumor objective response is evaluated according to RECIST 1.1 response criteria. Number of patients with beneficial clinical response (SD, PR and CR) are recorded in each group.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 n=5 Participants (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.	Cohort 3 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 200 mg daily 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. 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.	Cohort 4 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 300 mg daily 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. 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.
Number of Patients With Beneficial Clinical Response	5 Participants	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From beginning of study to the end of the 2nd cycle, and then at 16 weeks if the patient has stable disease or better.

Tumor objective response is evaluated according to RECIST 1.1 response criteria. Number of patients with beneficial clinical response (PR and CR) are recorded in each group.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 n=5 Participants (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.	Cohort 3 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 200 mg daily 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. 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.	Cohort 4 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 300 mg daily 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. 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.
Number of Patients With Tumor Objective Response	2 Participants	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From beginning of study to the end of the 2nd cycle, and then at 16 weeks if the patient has stable disease or better

Tumor assessment according to RECIST 1.1 was performed at the end of the second cycle, and then again at 16 weeks if the patient has stable disease or better. Scans may be performed every 8-12 weeks thereafter at the discretion of the investigators.

Outcome measures

Outcome measures
Measure	Cohort 1 n=7 Participants (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 n=5 Participants (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.	Cohort 3 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 200 mg daily 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. 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.	Cohort 4 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 300 mg daily 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. 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.
Progression Free Survival (in Months)	3.7 months Interval 1.2 to 7.3	2.4 months Interval 1.8 to 6.8	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From the end of treatment till 2 years following the last dose

Population: No patients were enrolled in Cohort 3 or Cohort 4 Two patients in Cohort 1 were alive at the end of follow up at 2 years after the last dose.

Survival status was monitored every 8 weeks for 2 years following the last dose

Outcome measures

Outcome measures
Measure	Cohort 1 n=8 Participants (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 n=6 Participants (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.	Cohort 3 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 200 mg daily 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. 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.	Cohort 4 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 300 mg daily 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. 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.
Overall Survival	16.1 months Interval 1.9 to 36.4	16.6 months Interval 4.3 to 32.5	—	—

Adverse Events

Cohort 1

Serious events: 3 serious events

Other events: 8 other events

Deaths: 2 deaths

Cohort 2

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cohort 4

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 n=8 participants at risk (each cycle is 28 days long) Everolimus 5mg daily on Mondays, Wednesdays, and Fridays Niraparib 100mg daily 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. 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.	Cohort 2 n=6 participants at risk (each cycle is 28 days long) Everolimus 5 mg daily on Mondays, Wednesdays, and Fridays Niraparib 200 mg daily 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. 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.	Cohort 3 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 200 mg daily 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. 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.	Cohort 4 (each cycle is 28 days long) Everolimus 5 mg daily Niraparib 300 mg daily 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. 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.
Blood and lymphatic system disorders Anemia	12.5% 1/8 • Number of events 1 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	33.3% 2/6 • Number of events 2 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4
Investigations Alkaline phosphatase increased	12.5% 1/8 • Number of events 1 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	0.00% 0/6 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4
General disorders Fatigue	25.0% 2/8 • Number of events 2 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	0.00% 0/6 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4
Vascular disorders Hypertension	12.5% 1/8 • Number of events 2 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	33.3% 2/6 • Number of events 2 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/8 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	16.7% 1/6 • Number of events 1 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4
Investigations Neutrophil count decreased	0.00% 0/8 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	16.7% 1/6 • Number of events 2 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4
Investigations Platelet count decreased	0.00% 0/8 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	33.3% 2/6 • Number of events 4 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4	— 0/0 • From beginning of treatment to 30 days after the last dose. The duration for collecting adverse events ranges from 2 months to 1 year, depending on the length of study treatment for each patient. no patients was enrolled in cohort 3 or cohort 4

Other adverse events

Additional Information

Dr. Casey Williams

Avera Cancer Institute

Phone: 6053223588

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place