Metastatic or Locally Advanced Solid Tumors
Conditions
Keywords
Cancer, BEZ235, BKM120, paclitaxel, trastuzumab
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.
Interventions
DRUGBEZ235 + paclitaxel
DRUGBKM120 + paclitaxel
DRUGBEZ235 + paclitaxel + trastuzumab
DRUGBKM120 + paclitaxel + trastuzumab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose limiting toxicities during the first cycle of treatment. | First treatment cycle (4 weeks) |
Secondary
| Measure | Time frame |
|---|---|
| Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers) | 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) |
| Treatment efficacy (response to treatment according to RECIST criteria) | From start of treatment until disease progression |
Countries
Belgium, Germany, Netherlands, Spain, Switzerland
Outcome results
None listed