Clinical trial NCT01339052
Conditions: Glioblastoma
Keywords: BKM120 Brain tumor
Sponsor: Patrick Y. Wen, MD
Start date: 2011-09-01; Completion date: 2019-02-01
Enrollment: 65 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
BKM120 is a newly discovered drug that has been used in other research studies. Information from those other research studies suggests that BKM120 may help to slow or stop the growth of malignant gliomas. The purpose of this study is to see how well BKM120 works in patients with malignant gliomas. Patients on this study will be treated in two groups: patients who are going to receive surgery and those who will not receive surgery. This study is trying to determine how effective BKM120 is in stopping cancer cells from growing. For patients receiving surgery the research will also try to determine if an effective level of BKM120 can penetrate the brain before surgery.

Detailed description:
OBJECTIVES:

Cohort 1

Primary Objectives

* Evaluate PI3K pathway modulation due to BKM120 in tumor tissue
* Evaluate BKM120 concentration in tumor tissue, plasma, and cerebrospinal fluid

Secondary Objectives

* Evaluate effects of BKM120 on tumor cell proliferation and tumor cell death
* Investigate the safety profile of BKM120 in this population
* Investigate pharmacokinetics of BKM120 in this population

Exploratory Objectives

* Correlate FDG-PET and FLT-PET with pharmacodynamic effects and 6-month progressive-free survival (PFS6)
* Determine the effects of BKM120 on primary GBM cell lines derived from participants and correlate with participant benefit from BKM120 treatment

Cohort 2

Primary Objective

* Investigate the treatment efficacy as measured by 6-month progressive-free survival (PFS6)

Secondary Objectives

* Investigate the radiographic response, progression free survival, overall survival
* Investigate the safety profile efficacy of BKM120 in this population

Exploratory Objectives

* Correlate benefit from BKM120 treatment with molecular genotype of tumor (using immunohistochemistry, mutation analysis and RNA expression profiling), and whole blood proteomics
* Correlate benefit from BKM120 treatment with circulating angiogenic biomarkers
* Utilize advance MRI (perfusion, permeability, diffusion imaging) to determine the effects of BKM120 on tumor vasculature and to correlate with benefit from BKM120 treatment

STATISTICAL DESIGN:

Cohort 1

The primary endpoint for Cohort 1 is modulation of PI3 kinase pathway based on change in immunohistochemistry (IHC) scoring for pAKT. Modulation in scoring as measured by reduction of staining intensity score of one degree or more was reported as a positive response to drug. This portion of the trial would be considered a success if 9 or more participants of 15 participants showed a response. There was a 94% chance of this occurring if the true response rate was 75% and only a 10% chance of this occurring if the true response rate was 40%.

Cohort 2

The primary endpoint for Cohort 2 is the proportion of participants progression free at 6 months (PFS6). Historical comparison data suggest that ineffective therapies in recurrent GBM have a PFS6 rate of approximately 9-16% (Wong 1999; Lamborn 2008). This trial was sized to differentiate between a 15% versus a 32% PFS6. With a total sample size of 50 participants, this design yields at least 90% power with a one sided alpha \< 0.1 to detect a true PFS6 rate of at least 32%. If the number of successes was ≥ 12, the therapy would be considered worthy of further study.

Arms: arm 1: Subjects scheduled for surgery

BKM120: 100 mg once daily, orally, for 8-12 days prior to surgery

Surgery: Surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Patients continued treatment until disease progression or unacceptable toxicity. arm 2: Subjects not candidates for surgery

BKM120: 100 mg once daily, orally, for 28-day cycles

Patients continued treatment until disease progression or unacceptable toxicity.
Interventions: intervention 1: BKM120 intervention 2: Surgery
Intervention descriptions: intervention 1: None intervention 2: Surgery

Protocol documents: