Phase I of BKM120/Olaparib for Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer
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Purpose
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 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 both of these agents BKM120 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 and olaparib is effective in treating your type of cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Ovarian Cancer Breast Cancer |
Drug: BKM120 and Olaparib |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Study of the Oral PI3kinase Inhibitor BKM120 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or Recurrent High Grade Serous Ovarian Cancer |
- Determine MTD for the Combination of BKM120 and Olaparib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of BKM120 and olaparib in patients with recurrent TNBC and HGSC.
- Determine the overall Safety and Observed Toxicities of combining BKM120 and Olaparib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]To determine the safety and observed toxicities of the combination of BKM120 and olaparib in this population
- Determine Pharmacokinetics of BKM120 and Olaparib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To measure the drug levels of both BKM120 and olaparib at different time points after they are started to see if either drug affects the metabolism and levels of the other. PK's samples will be drawn in duplicate (one set to be sent to Astrazeneca and the second set to Novartis). BKM120 and olaparib levels will be performed at the following timepoints:
- prior to taking both BKM120 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 activity of this combination at the MTD and RP2 dose [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine a preliminary anti-cancer activity of this combination at the MTD and RP2D dose. Anti-cancer activity of this combination will be measured by response rate by RECIST 1.1 in patients who have measurable cancer
- Exploratory Translational Endpoints [ Time Frame: 2 years ] [ Designated as safety issue: No ]
(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)
| Estimated Enrollment: | 56 |
| Study Start Date: | September 2012 |
| Estimated Study Completion Date: | December 2014 |
| Estimated Primary Completion Date: | August 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment Arm
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.
Other Names:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically or cytologically confirmed recurrent high grade serous ovarian cancer or triple negative breast cancer
- Subjects with recurrent, metastatic triple negative breast cancer must have had at least 1 chemotherapy regimen for metastatic breast cancer or have developed metastatic breast cancer within 1 year of completion of adjuvant chemotherapy
- Prior therapy for high grade serous ovarian cancer subjects must have included a first-line platinum-based regimen
- At least 4 weeks since prior radiation therapy, 3 weeks since prior chemotherapy and 6 weeks if the last regimen included BCNU or mitomycin C
- At least 4 weeks since any small-molecular kinase inhibitors or any other type of investigational agent
- Life expectancy of at least 4 months
- Able to swallow and tolerate oral medications
Exclusion Criteria:
- Evidence of bowel obstruction, abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of study entry
- Current dependency on IV hydration or total parental nutrition
- Diabetes mellitus unless well controlled
- Pregnant or breast feeding
- History of grade 3 or 4 toxicities with previous PI3kinase inhibitor or PARP inhibitor
- Current or active dermatologic diagnoses that would preclude interpretation of skin toxicities of BKM120
- Receiving any medications or substances that are strong inhibitors or inducers of CYP3A4
- History of cardiac dysfunction or disease
- Persistent toxicities (greater than or equal to CTCAE grade 2) caused by previous cancer therapy
- Major surgery within 14 days of starting study treatment
- Evidence of coagulopathy or bleeding diathesis
- History of major depressive episode, bipolar disorder, obsessive/compulsive disorder, schizophrenia, history of suicide attempt or ideation or homicide/homicidal ideation
- CTCAE grade 3 or greater anxiety
- Uncontrolled, intercurrent illness
- Known HIV positive and on combination antiretroviral therapy
- Receiving chronic treatment with steroids or another immunosuppressive agent
Contacts and Locations| Contact: Brian Lasonde | 617-632-3743 | blasonde@partners.org |
| Contact: Christin Whalen, RN | 617-632-7738 | cwhalen@partners.org |
| United States, Massachusetts | |
| Dana-Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Brian Lasonde 617-632-3743 blasonde@partners.org | |
| Contact: Christin Whalen, RN 617-582-7738 cwhalen@partners.org | |
| Principal Investigator: Ursula Matulonis, MD | |
| Massachusetts General Hospital | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Meghan Comeau 617-726-0491 mcomeau@mghihp.edu | |
| Principal Investigator: Michael Birrer, MD, PhD | |
| Beth Israel Deaconess Medical Center | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Kathryn Componeschi kcompone@bidmc.harvard.edu | |
| Contact: Robert Shaw 617-667-5987 rdshaw@bidmc.harvard.edu | |
| Principal Investigator: Gerburg Wulf, MD | |
| United States, New York | |
| Memorial Sloan-Kettering Cancer Center | Recruiting |
| New York City, New York, United States, 10065 | |
| Contact: Sara Kravetz 646-888-4423 kravetzs@mskcc.org | |
| Contact: Blair Station stationb@mskcc.org | |
| Principal Investigator: Katherine Bell-McGuinn, MD | |
| United States, Texas | |
| MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77230 | |
| Contact: Michael Garcia, RN 713-794-1421 mgarcia@mdanderson.org | |
| Principal Investigator: Shannon Westin, MD | |
| Principal Investigator: | Ursula A. Matulonis, M.D. | Dana-Farber Cancer Institute |
More Information
No publications provided
| Responsible Party: | Ursula A. Matulonis, MD, Principal Investigator, Dana-Farber Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT01623349 History of Changes |
| Other Study ID Numbers: | 12-159 |
| Study First Received: | June 7, 2012 |
| Last Updated: | March 29, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Dana-Farber Cancer Institute:
|
Recurrent High Grade Serous Triple Negative |
Additional relevant MeSH terms:
|
Breast Neoplasms Ovarian Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Endocrine Gland Neoplasms |
Ovarian Diseases Adnexal Diseases Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders |
ClinicalTrials.gov processed this record on May 21, 2013