A Trial of Oral BEZ235 and BKM120 in Combination With Paclitaxel With or Without Trastuzumab

A Phase Ib Multi-center, Open-label, 4-arm Dose-escalation Study of Oral BEZ235 and BKM120 in Combination With Weekly Paclitaxel in Patients With Advanced Solid Tumors and Weekly Paclitaxel/Trastuzumab in Patients With HER2+ Metastatic Breast Cancer

The purpose of the trial is to determine the maximum tolerated dose (MTD) of BEZ235 and BKM120 in combination with weekly paclitaxel and weekly paclitaxel/trastuzumab.

Inclusion Criteria:

• Adult patients with metastatic or locally advanced solid tumors, for whom weekly paclitaxel treatment is indicated (BEZ235-paclitaxel /BKM120-paclitaxel treatment)
• HER2+ metastatic or locally advanced breast cancer patients eligible for weekly paclitaxel and trastuzumab (BEZ235-paclitaxel-trastuzumab /BKM120-paclitaxel-trastuzumab treatment)
• Adult patients (≥ 18 years) (males, females)
• World Health Organization (WHO) performance status ≤ 2
• Adequate bone marrow function:
• Adequate hepatic and renal function:

Exclusion Criteria:

• Patients with primary central nervous system (CNS) tumor or CNS tumor involvement. However, patients with a metastatic CNS lesion may participate in this trial, if the patient is > 4 weeks from therapy (including radiation and/or surgery) completion, clinically stable with respect to the tumor at the time of study entry, and not receiving enzyme-inducing antiepileptic drugs or corticosteroid therapy or taper, as treatment of the brain metastases
• Patients who have received prior systemic anticancer therapy within the following time frames
• Cyclical chemotherapy: ≤ 3 weeks before study treatment (6 weeks for patients treated with nitrosoureas)
• Biological therapy: ≤ 4 weeks before study treatment, except treatment with trastuzumab (both parts of the trial)
• Investigational drug: ≤ 4 weeks before study treatment
• Patients who have undergone major surgery ≤ 4 weeks before study treatment
• Patients receiving chronic treatment with corticosteroids or other immunosuppressive agents
• Patients with uncontrolled, unmanageable, treatment-refractory diabetes mellitus
• Active or history of major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, history of suicide attempt or ideation, or homicide, as judged by the investigator and/or based on recent psychiatric assessment

Other protocol-defined inclusion/exclusion criteria may apply