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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Metastatic or Locally Advanced Solid Tumors

Intervention / Treatment
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* Drug: BEZ235 + paclitaxel
* Drug: BKM120 + paclitaxel
* Drug: BEZ235 + paclitaxel + trastuzumab
* Drug: BKM120 + paclitaxel + trastuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BEZ235 + paclitaxel<br> | Drug: BEZ235 + paclitaxel<br> <br> |
| Experimental: BKM120 + paclitaxel<br> | Drug: BKM120 + paclitaxel<br> <br> |
| Experimental: BEZ235 + paclitaxel + trastuzumab<br> | Drug: BEZ235 + paclitaxel + trastuzumab<br> <br> |
| Experimental: BKM120 + paclitaxel + trastuzumab<br> | Drug: BKM120 + paclitaxel + trastuzumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose limiting toxicities during the first cycle of treatment. |  | First treatment cycle (4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of safety events during the whole treatment period (until progression of disease). |  | From start of treatment until disease progression | 
| pharmacokinetics of BEZ235, BKM120 and paclitaxel given in combination, on Day 1, 8 and 22. |  | First treatment cycle (4 weeks) | 
| Treatment efficacy (response to treatment according to RECIST criteria) |  | From start of treatment until disease progression | 
| Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers) |  | From start of treatment until disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, BEZ235, BKM120, paclitaxel, trastuzumab