BKM120 For Triple Negative Breast Cancer

Study plan Two investigator-initiated protocols (one for US, one for Spain) will be enrolling in parallel. The first 50 participants will be recruited concurrently in US and Spain.

Stage 1 Stage 1 will include up to 50 participants with advanced TN disease. Available tumor block is required in all participants per inclusion criteria. Analysis of this tumor block will be used for correlation of predictive markers and clinical response in order to define potential subpopulation that benefit from BKM120. In Stage 1, all participants will have biopsies done at baseline, cycle 1 day 28/cycle 2 day 1 and end of treatment to analyze drug effect in the PI3K and mitogen-activated protein kinases (MAPK) pathway. This will aid to understand the pharmacodynamic effects of BKM120 in tumors with similar genetic background (triple negative disease). The enrollment of Stage 1 will ensure that at least 10 paired evaluable biopsies are obtained. After the enrollment of the first 29 evaluable subjects enrolled overall in Stage 1 (considering the US and the Spanish protocol), the Steering Committee will perform an interim analysis of safety and efficacy. If absolutely no activity is observed, the clinical trial will close and no more subjects will be enrolled. If there are early signs of activity (one patient or more achieving clinical benefit response), enrollment will proceed until 50 participants are enrolled in Stage 1. After 50 patients have been enrolled, we will analyze preliminary responses to treatment depending on the molecular status of each patient.

Stage 2 Were the trial to continue at the end of Stage 1, 50 participants would have been treated and their clinical status and response to therapy will be available. Also, paraffin blocks from these participants will have been analyzed for predictive markers of treatment effect. If there is clinical activity observed in Stage 1 and this analysis shows preliminary signs of response in a subpopulation based on the presence or absence of tumor PI3K pathway alterations, participant pre-selection may be implemented for Stage 2 (justified in an amendment before proceeding to Stage 2.

Inclusion criteria

• Pathologically and radiologically confirmed metastatic triple negative breast cancer
• Up to two prior lines of chemotherapy for metastatic breast cancer
• Availability of a representative tumor specimen
• At least one measurable lesion

Exclusion criteria

• Have received previous treatment with PI3K inhibitors
• Symptomatic central nervous system (CNS) metastases (controlled and asymptomatic CNS metastases are acceptable)
• Concurrent malignancy or has a malignancy within 3 years of study enrollment
• Any of the following mood disorders: active major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, history of suicidal attempt or ideation, homicidal ideation, greater than or equal to Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 anxiety
• Concurrently using other approved or investigational antineoplastic agent and/or chemotherapy within 21 days prior to enrollment in this study
• Has received radiation therapy within 28 days prior to enrollment in this study or has not recovered from side effects of such therapy
• Major surgery within 28 days of starting therapy or has not recovered from major side effects of a previous surgery
• Poorly controlled diabetes mellitus
• History of cardiac dysfunction
• Currently receiving treatment with QT prolonging medication and the treatment cannot be discontinued or switched to a different medication
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120
• Receiving chronic treatment with steroids or another immunosuppressive agent
• Other concurrent severe and/or uncontrolled medical condition that would contraindicate participation in this study
• History of non-compliance to a medical regimen
• Currently being treated with drugs known to be moderate or strong inhibitors or inducers of isoenzyme Cytochrome P450, family 3, subfamily A (CYP3A)
• Known history of human immunodeficiency virus (HIV)
• Pregnant or breastfeeding
• Unwilling to observe total abstinence or to use double barrier method for birth control throughout trial