Phase II Study of BKM120 for Subjects With Recurrent Glioblastoma

Inclusion Criteria

• Participants must be able to understand and be willing to sign a written informed consent document.
• Subjects must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
• Participants must be at least 18 years old.
• Participants must have a Karnofsky performance status (KPS) ≥ 60. Nature of illness and treatment history
• Participants must have histologically confirmed glioblastoma or variants. Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
• Participants may have had treatment for no more than 1 prior relapse(NOTE: Relapse is defined as progression following initial therapy (i.e., radiation ± chemotherapy)). The intent therefore is that patients had no more than 2 prior therapies (initial and treatment for 1 relapse). If the participant had a surgical resection for relapsed disease and no antitumor therapy was instituted for up to 12 weeks, and the participant undergoes another surgical resection, this is considered as a second relapse. For participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse).
• Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
• For Cohort 2, CT or MRI within 14 days prior to start of study drug. MRIs should include vascular imaging when possible. For Cohort 2, corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the screening MRI or CT scan and the start of treatment, a new baseline MRI or CT is required. For Cohort 1 subjects, CT or MRI should be performed ideally within 14 days prior to study registration, but because the screening MRI for this subset of subjects will not be used for evaluation of response, it is acceptable for this MRI/CT to have been performed greater than 14 days prior to registration if unavoidable. Furthermore, for this same reason, fluctuation in corticosteroid dose around this MRI does not warrant repeat scan so long as there is documented unequivocal evidence of tumor progression available.
• For Cohort 2, Immunohistochemical or genetic analysis on tumor tissue from a prior surgery must demonstrate activation of the PI3K pathway through one of the following: PIK3CA mutation of PIK3R1 mutation, PTEN negativity ( 40 mIU/mL and estradiol 8%) or poorly controlled steroid-induced diabetes mellitus (glycosylated hemoglobin > 8%)
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or extensive small bowel resection). Participants with unresolved diarrhea will be excluded as previously indicated.
• Participants who have undergone major systemic surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.