Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer
|ClinicalTrials.gov Identifier: NCT01623349|
Recruitment Status : Active, not recruiting
First Posted : June 20, 2012
Last Update Posted : March 23, 2017
This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational combination of drugs. Phase I studies also try to define the appropriate dose of the investigational combination to use for further studies. "Investigational" means that the combination of these drugs is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved either of these drugs nor the combination of being tested for use in patients, including people with your type of cancer.
BKM120, BYL719 and olaparib are drugs that may stop cancer cells from growing abnormally. These drugs when combined in laboratory experiments with animals, have demonstrated anti-cancer activity. Information from these other research studies suggests that the following agents BKM120, BYL719 and olaparib, may help to shrink tumor cells in the types of cancers being studied in this research study.
In this research study, the investigators are looking for the highest dose that can be given safely and also to see if the combination of BKM120 or BYL719 and olaparib is effective in treating your type of cancer.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Breast Cancer||Drug: BKM120 and Olaparib Drug: BYL719 and Olaparib||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||118 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer|
|Study Start Date :||September 2012|
|Estimated Primary Completion Date :||August 2017|
|Estimated Study Completion Date :||December 2017|
U.S. FDA Resources
Experimental: Arm BKM
BKM120 and Olaparib
Drug: BKM120 and Olaparib
Olaparib twice daily (starting dose 50 mg) and BKM120 once daily (starting dose 40 mg). Both drugs are given orally.
Experimental: Arm BYL
BYL719 and Olaparib
Drug: BYL719 and Olaparib
Olaparib twice daily (starting dose 100 mg) and BYL719 once daily (starting dose 250 mg). Both drugs are given orally.
- Determine MTD and RP2D of the Combination of BKM120 and Olaparib, and the Combination of BYL719 and Olaparib [ Time Frame: 2 years ]To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of BKM120 and olaparib, and the combination of BYL719 and olaparib in patients with recurrent TNBC and HGSC.
- Determine the overall Safety and Observed Toxicities of combining BKM120 and Olaparib, and combining BYL719 and Olaparib [ Time Frame: 2 years ]To determine the safety and observed toxicities of the combination of BKM120 and olaparib, and the combination of BYL719 and olaparib in this population
- Determine Pharmacokinetics of BKM120 and Olaparib, and BYL719 and Olaparib [ Time Frame: 2 years ]
To measure the drug levels of both BKM120 and olaparib, and both BYL719 and olaparib at different time points after they are started to see if either drug affects the metabolism and levels of the other. PK samples will be drawn in duplicate (one set to be sent to Astrazeneca and the second set to Novartis). BKM120 (or BYL719) and olaparib levels will be performed at the following timepoints:
- prior to taking both BKM120 (or BYL719) and olaparib cycle 1, day 1.
- Cycle 1, day 8: prior to dosing, 1, 2, 4, and 8 hours post am dosing.
- Cycle 1, day 15: prior to dosing, 1, 2, 4, and 8 hours post am dosing.
- Determine preliminary activities of these combinations at the MTD and RP2 dose [ Time Frame: 2 years ]To determine a preliminary anti-cancer activities of these combinations at the MTD and RP2D dose. Anti-cancer activities of these combinations will be measured by response rate by RECIST 1.1 in patients who have measurable cancer
- Exploratory Translational Endpoints [ Time Frame: 2 years ]
(A) To determine the downstream signaling effects of the PI3-kinase pathway whenboth PI3-kinase and PARP are inhibited.
(B) To determine BRCA1 immnostaining, BRCA1 promoter hypermethylation and somatic mutations in BRCA1 and BRCA2 in archived formalin fixed paraffin embedded (FFPE) tissue and any new available tissues (pre- or post-treatment biopsies and biopsies or other tumor colelction for clinical care at the time of or following tumor progression)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01623349
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York City, New York, United States, 10065|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77230|
|Principal Investigator:||Ursula A. Matulonis, M.D.||Dana-Farber Cancer Institute|