This clinical study will assess the doses of BKM120 appropriate for patients with newly diagnosed glioblastoma when given in combination with radiotherapy and temozolomide.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
The investigational drug, BKM120, will be supplied as 10-mg and 50-mg hard gelatin capsules. BKM120 will be administered on a once daily dosing schedule at a dose of 40 mg, or 60 mg, or 80 mg, or 100 mg (p.o.), in combination with the approved dosing of temozolomide and SoC delivery of cranial irradiation for GBM. The patient will be dosed with BKM120 on a flat scale of mg/day and the dose of BKM120 will not be adjusted to body weight or body surface area. Patients should not eat for 2 hours after the administration of BKM120. Temozolomide in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg capsules will be administered in combination with the investigational drug BKM120.
The investigational drug, BKM120, will be supplied as 10-mg and 50-mg hard gelatin capsules. BKM120 will be administered on a continuous once daily dosing schedule at a dose of 40 mg, or 60 mg, or 80 mg, or 100 mg (p.o.), in combination with the approved dosing of temozolomide and SoC delivery of cranial irradiation for GBM. The patient will be dosed with BKM120 on a flat scale of mg/day and the dose of BKM120 will not be adjusted to body weight or body surface area. Patients should not eat for 2 hours after the administration of BKM120. Temozolomide in 5 mg, 20 mg, 100 mg, 140 mg, 180 mg or 250 mg capsules will be administered in combination with the investigational drug BKM120.
Highlands Oncology Group Highlands Oncology
Fayetteville, Arkansas, United States
Dana Farber Cancer Institute SC (1)
Boston, Massachusetts, United States
University of Texas/MD Anderson Cancer Center MD Anderson DeGrout
Houston, Texas, United States
Novartis Investigative Site
Dose Limiting Toxicity (DLT)
Per DLT criteria as defined in protocol
Time frame: Concomitant phase (42 days), adjuvant phase cycle 1 (28-day cycle), adjuvant phase cycles 2 (28-day cycle)
No of participants with Adverse events based on abnormal laboratory results, abnormal electrocardiogram (ECG) findings
Per common terminology criteria for adverse events (CTCAE) criteria (version 4.0)
Time frame: Baseline, 30 days post the last BKM120 treatment
Objective response rate (ORR)
Antitumor activity will be assessed using the Neuro-Oncology Working Group updated response assessment criteria for high grade gliomas - per RANO criteria.
Time frame: Baseline, 18 months after first BKM120 treatment
Progression free survival (PFS)
Per patient survival follow up feedbacks
Time frame: at 12 months and at 18 months
Overall survival (OS)
Per patient survival follow up feedbacks
Time frame: Until death or consent withdrawal
Plasma concentration-time profiles and basic pharmacokinetic parameters of BKM120 and temozolomide (Cmax, tmas, AUC, half-life)
Standard bioanalytical-pharmacokinetic (PK) analysis on PK samples for BKM120 and temozolomide.
Time frame: baseline, Day 1, 8, 15, 28 in concomitant phase, Cycle 1 Day 1, 5 and Cycle 2 Day1, 5 at adjuvant phase (28-day per cycle)
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Melbourne, Victoria, Australia
Novartis Investigative Site
Hamilton, Ontario, Canada
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
Madrid, Spain