Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer

Inclusion Criteria:

* World Health Organization (WHO) Performance Status of ≤ 2
* Patients with HER2+ breast cancer by local laboratory testing (immunohistochemistry \[IHC\] 3+ staining or fluorescence in situ hybridization \[FISH\] confirmation for IHC 2+ and 1+)
* Documented tumor resistance to trastuzumab:

  * Recurrence while on trastuzumab or within 12 months since the last infusion for patients who received trastuzumab as adjuvant treatment
  * Progression while on or within 4 weeks since the last infusion of trastuzumab for patients who received trastuzumab for metastatic disease.
* Documented evidence of progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) on trastuzumab-based therapy defined as:

  * Phase Ib: at any time before study entry
  * Phase II: within 16 weeks before date of first dosing
* Received at least 1 but no more than 4 prior anit-HER2 based regimens including at least 1 regimen containing trastuzumab (adjuvant or neo-adjuvant trastuzumab will be considered as one prior regimen). HER2 directed therapies are defined as comprising trastuzumab, lapatinib, and trastuzumab-DM1 (T-DM1) only.

  • Phase II only: trastuzumab, T-DM1 or lapatinib must be part of the most recent line of therapy
* Previous lines of cytotoxic chemotherapy:

  * Phase Ib: no more than 4 lines of cytotoxic chemotherapy
  * Phase II: no more than 3 lines of cytotoxic chemotherapy

Measurable disease:

* Phase Ib: patient has at least one measurable lesion or non-measurable disease as defined per RECIST
* Phase II: patient has at least one measureable lesion as defined per RECIST

\|\| Specific Inclusion Criteria for patients in BM cohorts:

* Patient has evidence of progressing brain metastases and/or new metastatic brain lesion(s) without leptomeningeal disease.
* Patient has received prior WBRT and/or SRS at at \>28 and \>/= 14 days, respectively, prior to starting study drug and the patient must have recovered from the side effects of the therapy
* WHO performance status of \</=1
* PT INR \</= 1.5
* Any number of prior HER2-directed and cytotoxic regimens, and the most recent line may be any type of anti-neoplastic therapy

\|\| Exclusion Criteria:

* Patients with untreated brain metastases
* Patients with acute or chronic liver, renal disease or pancreatitis
* Patients with any peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2
* Patients with a history of mood disorders or ≥ CTCAE grade 3 anxiety
* Patient with clinical manifest diabetes mellitus or steroid-induced diabetes mellitus

\|\| Specific Exclusion Criteria for patients in BM cohorts

* Prior treatment with capecitabine
* Patient has known dihydropyrimidine dehydrogenase (DPD) deficiency
* Patient is currently receiving treatment with EIAED
* Other protocol-defined inclusion/exclusion criteria may apply