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Phase I of BKM120/Olaparib for Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Ursula A. Matulonis, MD, Dana-Farber Cancer Institute Identifier:
First received: June 7, 2012
Last updated: September 5, 2014
Last verified: September 2014

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

Resource links provided by NLM:

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • 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:

    1. prior to taking both BKM120 and olaparib cycle 1, day 1.
    2. Cycle 1, day 8: prior to dosing, 1, 2, 4, and 8 hours post am dosing.
    3. 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 2016
Estimated Primary Completion Date: August 2016 (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:
  • Olaparib (NSC 747856)
  • BKM120 (IND 102823)

  Show Detailed Description


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01623349

Contact: Christin Whalen, RN 617-582-7738
Contact: Philippa Quy 617-632-6944

United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Susan McIntyre    617-667-1940   
Contact: Aaron Weitz    617-667-5987   
Principal Investigator: Gerburg Wulf, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Christin Whalen, RN    617-582-7738   
Contact: Kristin Meegan    617-632-6617   
Principal Investigator: Ursula Matulonis, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Tina Atkinson    617-643-5150   
Principal Investigator: Michael Birrer, MD, PhD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York City, New York, United States, 10065
Contact: Katherine Bell-McGuinn, MD    646-888-4221   
Principal Investigator: Katherine Bell-McGuinn, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77230
Contact: Shannon Westin, MD    713-794-4314      
Principal Investigator: Shannon Westin, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
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 Identifier: NCT01623349     History of Changes
Other Study ID Numbers: 12-159
Study First Received: June 7, 2012
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
High Grade
Triple Negative

Additional relevant MeSH terms:
Breast Neoplasms
Ovarian Neoplasms
Triple Negative Breast Neoplasms
Adnexal Diseases
Breast Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms by Site
Ovarian Diseases
Skin Diseases
Urogenital Neoplasms processed this record on November 27, 2014