Combination of BKM120 and Bevacizumab in Refractory Solid Tumors and Relapsed/Refractory Glioblastoma Multiforme
In this phase I/II study, the investigators plan to evaluate the feasibility and efficacy of the combination of BKM120, an oral inhibitor of PI3 kinase, and bevacizumab in the treatment of patients with relapsed/refractory GBM. In the Phase I part of the trial, the optimal BKM120 dose to be administered with a standard dose of bevacizumab will be determined in patients with refractory solid tumors. Although it is unlikely that the concurrent administration of bevacizumab will alter the pharmacokinetics of BKM120, limited pharmacokinetic sampling will be performed on all patients treated during the Phase II portion of the study. Assuming this combination is feasible, the Phase II portion of the study will proceed, using the doses determined in the Phase I portion. In the phase II portion, eligible patients will be limited to those with recurrent/progressive GBM following 1st line combined modality therapy.
|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.
- Progression Free Survival (PFS) [ Time Frame: 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:||December 2015 (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.
The phase I study will determine the MTD of BKM120 when combined with bevacizumab. The Phase I portion will follow a standard dose escalation design, beginning with dose level 1. The sequence of dose escalation for BKM120 and bevacizumab is based on a starting dose of 60 mg/day for BKM120 (i.e. 50% of the MTD of BKM120 when administered as a single agent). A maximum of three BKM120 dose levels will be evaluated. Bevacizumab will be fixed at 10 mg/kg IV and will be administered every two weeks. Approximately 18 patients will be enrolled during the Phase I portion to establish the MTD.
In the Phase II portion of this study, patients with relapsed/refractory GBM following first line therapy will receive treatment with the BKM120/bevacizumab combination. Limited BKM120 pharmacokinetic evaluation will be performed on all patients treated during the Phase II portion 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
|Contact: John Hainsworth, M.D.||firstname.lastname@example.org|
|Contact: Trials Infoemail@example.com|
|United States, Connecticut|
|Yale School of Medicine||Recruiting|
|New Haven, Connecticut, United States, 06520|
|United States, Florida|
|Florida Cancer Specialists||Recruiting|
|Ft. Myers, Florida, United States, 33916|
|Florida Hospital Cancer Institute||Recruiting|
|Orlando, Florida, United States, 32804|
|Woodlands Medical Specialists||Recruiting|
|Pensacola, Florida, United States, 32503|
|Florida Cancer Specialists||Recruiting|
|St. Petersburg, Florida, United States, 33705|
|United States, Maryland|
|Center for Cancer and Blood Disorders||Recruiting|
|Bethesda, Maryland, United States, 20817|
|United States, Michigan|
|Grand Rapids Oncology Program||Recruiting|
|Grand Rapids, Michigan, United States, 49503|
|Principal Investigator: Gilbert Padula, MD|
|United States, Missouri|
|St. Louis Cancer Care||Recruiting|
|Chesterfield, Missouri, United States, 63017|
|United States, Nebraska|
|Nebraska Methodist Hospital||Recruiting|
|Omaha, Nebraska, United States, 68114|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|United States, Virginia|
|Peninsula Cancer Institute||Completed|
|Newport News, Virginia, United States, 23601|
|Virginia Cancer Institute||Completed|
|Richmond, Virginia, United States, 23235|
|Study Chair:||John Hainsworth, MD||SCRI Development Innovations, LLC|