(BKM120 2202) A Randomized, Double-Blind, Placebo Controlled, Phase II/III Study of BKM120 Plus Paclitaxel in Patients with HER2 Negative Inoperable Locally advanced or Metastatic Breast Cancer, With or without P13K Pathway Activation.

Study ID
STU 082012-085

Cancer Related

Healthy Volunteers

Study Sites

Todd Morgan

Principal Investigator
Barbara Haley


This study will evaluate the efficacy and safety of BKM120 in combination with weekly paclitaxel compared to BKM 120 matching placebo with weekly Paclitaxel in patients with HeR2 negative first line inoperable locally advanced or metastaic breast cancer survival assessments will be performed

Patients will be randomized to receive either BKM120 100 mg daily in combination with weekly paclitaxel or BKM120 matching placebo daily in combination with weekly paclitaxel. )

The first 100 patients irrespective of treatment assignment will have PK samples taken: the first 20 patients will have full PK sampling taken, and the next 80 patients will have sparse PK sampling. a DMC will monitor patient safety and review the results of the full PK sample analysis.

Tumor assessments will be performed every 8 weeks until radiological progression (assessed by ReCiST 1.1). Patients will continue to receive study treatment until disease progression (assessed by ReCiST 1.1), unacceptable toxicity, death or discontinuation from study treatment for any other reason.

all patients, regardless of reason for treatment discontinuation will be followed for safety for 30 days after the last dose of study treatment. all patients who discontinue from study treatment due to disease progression must have their progression clearly documented according to the criteria specified in ReCiST v1.1. if a patient did not discontinue study treatment due to disease progression, death, start of new anti-neoplastic therapies, lost to follow-up, or withdrawal of consent to efficacy follow-up, then tumor assessments should continue to be performed every 8 weeks until the start of new anti-cancer therapy, disease progression, death, lost to follow-up or withdrawn consent to efficacy follow-up. all patients will be followed for survival status every 3 months regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up). additional survival assessments
may be performed outside the 3 months follow-up schedules if a survival update is required for an interim assessment to meet safety or regulatory needs.

Participant Eligibility

Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Patient is an adult, female >= 18 years old at the time of informed consent
2. Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
3. Patient has radiologic or objective evidence of inoperable locally advanced, or metastatic
breast cancer
4. Patient has HER2 negative disease (based on most recently analyzed biopsy) defined as a
negative in situ hybridization by approved test or an IHC status of 0, 1+ or 2+ (if IHC 2+,
a negative in situ hybridization test is required) by local laboratory testing
5. Patient has a known PI3K pathway status (activated or non-activated based on results from
a Novartis designated laboratory prior to the start of treatment)

* A representative archival or fresh tumor biopsy must be shipped to a Novartis
designated laboratory for profiling and results obtained prior to randomization
through IRT

* Note: one block or minimum 20 unstained slides are required to determine the PI3K
activation status. Whenever possible 25 unstained slides is preferred.
6. Patient has a known ER/PgR status (either positive or negative) by local laboratory testing
7. Patient has measurable or non-measurable disease according to RECIST 1.1 criteria
8. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status <= 1
which the investigator believes is stable at the time of screening
9. Patient has adequate bone marrow and organ function as defined by the following
laboratory values:
a. Absolutely Neutrophil Count (ANC) >= 1.5 x 109/L
b. Platelets >= 100 x 109/L
c. Hemoglobin >= 9.0 g/dL
d. INR <= 1.5
e. Potassium and calcium (corrected for albumin), within normal limits for the
f. Serum creatinine <= 1.5 x ULN and/or creatinine clearance > 45 mL/min
g. Total serum bilirubin < ULN (or <= 1.5 x ULN if liver metastases are present; or total
bilirubin <= 3.0 x ULN with direct bilirubin within normal range in patients with well
documented Gilbert[Single Quote]s Syndrome, which is defined as presence of several episodes of
unconjugated hyperbilirubinemia with normal results from CBC count (including
normal reticulocyte count and blood smear), normal liver function test results, andabsence of other contributing disease processes at the time of diagnosis (see Appendix
in the final protocol)]
h. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 1.5x ULN
(or < 3.0 x ULN if liver metastases are present)
i. Fasting plasma glucose (FPG) <= 120mg/dL or <= 6.7 mmol/L
j. HbA1c <= 8 %
10. Patient is able to swallow and retain oral medication
11. Patient has signed the Informed Consent (ICF) prior to any screening procedures being