A Trial of Oral BEZ235 and BKM120 in Combination With Paclitaxel With or Without Trastuzumab
Phase 1
Completed
- Conditions
- Metastatic or Locally Advanced Solid Tumors
- Interventions
- Registration Number
- NCT01285466
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 110
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BEZ235 + paclitaxel BEZ235 + paclitaxel - BEZ235 + paclitaxel + trastuzumab BEZ235 + paclitaxel + trastuzumab - BKM120 + paclitaxel + trastuzumab BKM120 + paclitaxel + trastuzumab - BKM120 + paclitaxel BKM120 + paclitaxel -
- Primary Outcome Measures
Name Time Method Incidence of Dose limiting toxicities during the first cycle of treatment. First treatment cycle (4 weeks)
- Secondary Outcome Measures
Name Time Method Treatment efficacy (response to treatment according to RECIST criteria) From start of treatment until disease progression 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) Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers) From start of treatment until disease progression
Trial Locations
- Locations (1)
Novartis Investigative Site
🇨🇭St. Gallen, Switzerland