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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

Phase 1
18 Years
Open (Enrolling)
Ovarian Cancer, Breast Cancer

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Trial Information

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

During this study, additional tests will be performed on a sample of your original tumor
that has been stored in your institution's tissue banks. These tests will be performed on
tumor tissue samples from previous biopsies or surgeries for your cancer. The research done
on these samples will involve looking at DNA and proteins in your cancer to see if
researchers can learn more about your type of cancer and understand how this combination of
drugs might work on your tumor. Testing of this sample will not require you to undergo any
additional research procedures.

Approximately 2 tablespoons of blood will be collected for research testing. This testing
will involve looking at DNA and proteins in your blood to compare them with those seen in
your cancer. This will be drawn before you begin taking the study drug.

Participants in the dose expansion portion of the study may be asked to have a tumor biopsy
done. The dose expansion phase occurs after the appropriate dose for the combination of
BKM120 and Olaparib has been determined. Your doctor will tell you if you are in this
portion of the trial. Before and after you begin taking BKM120 and olaparib, your doctor may
also ask you to participate in an optional study where you would have tumor biopsies done.

You may also participate in an optional blood test for the BRCA gene. Approximately 2
teaspoons of blood will be taken for this test. The BRCA gene test is a blood test that uses
DNA analysis to see changes in either one of two breast cancer genes, known as BRCA1 or
BRCA2. After having a BRCA gene test performed, you learn whether you carry an inherited
BRCA gene mutation. If your blood is tested for the BRCA gene, the results will be reported
to your study doctor who will share the results with you and provide information related to
your personal risk of breast cancer. Having a BRCA gene mutation is rare, occurring in only
about 1 in 1000 people. Inherited BRCA gene mutations are responsible for less than 5 to 10
percent of breast cancers and about 10 to 15 percent of ovarian cancers.

Participation in the tumor biopsy and blood test for the BRCA gene are optional, and whether
you consent or refuse to undergo these additional tests will not affect your participation
in the main research study.

Since the investigators are looking for the highest dose of the study drug that can be
administered safely without severe or unmanageable side effects in participants that have
high grade serious ovarian cancer or triple negative breast cancer, not everyone who
participates in this research study will receive the same dose of the study drug. The dose
you get will depend on the number of participants who have been enrolled in the study before
you and how well they have tolerated their doses.

Both drugs are in oral form. If you take part in this research study, you will be given a
study dosing calendar for each drug for each treatment cycle. Each treatment cycle lasts 4
weeks. BKM120 should be taken once daily in the morning, one hour after a light meal.
Olaparib should be taken twice a day continuously, about twelve hours apart. The olaparib
morning dose should be taken at the same time as BKM120 one hour after a light meal. The
evening dose can also be taken one hour after a light meal or on an empty stomach either 1
hour before or 2 hours after meals. If you vomit either or both medications, record this on
your diary and do not take another dose that day.

The investigators will assess your tumor by CT or MRI scan every 8 weeks. During Cycle 1,
you will come into the clinic every week, and during cycle 2, you will come into clinic
every 2 weeks. For all cycles thereafter, you will come in once every 4 weeks.

During study visits you will undergo some or all of the following: evaluation of performance
status, recording of any healthy problems, physical exam including vital signs, list of
medications taken since last visit, questionnaire to evaluate anxiety and depression,
routine blood tests, research blood tests, Electrocardiogram and optional biopsy.

You will remain in this research study as long as you are benefitting from study treatment.
If you are removed from the research study for any reason you may be followed for up to one

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine MTD for the Combination of BKM120 and Olaparib

Outcome Description:

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.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Ursula A. Matulonis, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

September 2012

Completion Date:

December 2014

Related Keywords:

  • Ovarian Cancer
  • Breast Cancer
  • Recurrent
  • High Grade
  • Serous
  • Triple Negative
  • Breast Neoplasms
  • Ovarian Neoplasms



MD Anderson Cancer Center Houston, Texas  77030-4096
Memorial Sloan-Kettering Cancer Center New York, New York  10021
Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Massachusetts General Hospital Boston, Massachusetts  02114-2617