Combination of BKM120 and Bevacizumab in Refractory Solid Tumors and Relapsed/Refractory Glioblastoma Multiforme
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of the Combination of BKM120 and Bevacizumab in Patients With Refractory Solid Tumors (Phase I) and Relapsed/Refractory Glioblastoma Multiforme (Phase II)|
- Number of patients experiencing a dose-limiting toxicity (DLT) as a Measure of Safety and Tolerability [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Phase 1: The optimal dose of BKM120 to administer in combination with standard dose bevacizumab determined as the highest dose at which ≤1 of 6 patients experiences a DLT assessed using NCI CTCAE v4.0.
- Median Progression-Free Survival [ Time Frame: every 8 weeks, estimated 24 months ] [ Designated as safety issue: No ]Phase 2: Measured from the date of first protocol treatment until date of tumor progression or death occurs, or date of last adequate tumor assessment analyzed using Kaplan-Meier methods..
- Frequency and severity of adverse events as a measure of toxicity. [ Time Frame: every 8 weeks, projected 24 months ] [ Designated as safety issue: Yes ]Safety will be evaluated for patients in Phase I and II based on NCI CTCAE v4.0 criteria.
- Overall Survival (OS) [ Time Frame: every 8 weeks, projected 24 months ] [ Designated as safety issue: No ]Measured as the interval from first study treatment until date of death, or date last known alive.
- Overall Response Rate [ Time Frame: every 8 weeks, projected 24 months ] [ Designated as safety issue: No ]Proportion of patients with confirmed complete or partial responses (CR or PR) according to RECIST v1.1 criteria.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
BKM 120 orally (PO) once daily (dose to be determined) Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks
BKM 120 orally (PO) once daily - 60mg was the maximum tolerated dose (MTD) determined in Phase I Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks
Bevacizumab 10 mg/kg IV every 2 weeks
Other Name: AvastinDrug: BKM120
BKM120 orally (PO) once daily
Other Name: Buparlisib
This is an open-label, non-randomized Phase I study of patients with advanced refractory solid tumors followed by a Phase II study for the second-line treatment of patients with relapsed/refractory glioblastoma multiforme.
In the phase I part of the study the MTD of BKM120 when combined with bevacizumab was determined to be 60 mg/day. In the Phase II part of this study, patients with relapsed/refractory GBM following first line therapy are being treated with the BKM120/bevacizumab combination. Limited BKM120 pharmacokinetic evaluation will be performed on all patients treated during this part of the study. Patients will be reevaluated for response to treatment after 2 cycles (8 weeks). Patients with objective response or stable disease will continue treatment, with subsequent reevaluations every 8 weeks, until disease progression or unacceptable toxicity occurs.
Two populations of patients with relapsed/refractory GBM will be treated in the Phase II trial: 1) patients with no previous exposure to bevacizumab (N= 55) and 2) patients who received bevacizumab as part of first-line combined modality treatment (N= 20).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01349660
|United States, Connecticut|
|Yale School of Medicine|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|Florida Cancer Specialists|
|Ft. Myers, Florida, United States, 33916|
|Florida Hospital Cancer Institute|
|Orlando, Florida, United States, 32804|
|Florida Cancer Specialists|
|St. Petersburg, Florida, United States, 33705|
|United States, Maryland|
|Center for Cancer and Blood Disorders|
|Bethesda, Maryland, United States, 20817|
|United States, Michigan|
|Grand Rapids Oncology Program|
|Grand Rapids, Michigan, United States, 49503|
|United States, Nebraska|
|Nebraska Methodist Hospital|
|Omaha, Nebraska, United States, 68114|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||John Hainsworth, MD||SCRI Development Innovations, LLC|