Conditions: c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM
Keywords: Glioblastoma multiforme (GBM), glioblastoma, Grade IV Astrocytoma, brain tumor, brain cancer, giant cell glioblastoma, gliosarcoma
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 43
Healthy volunteers: no

Brief summary:
The study assessed the safety and the dose of the combination of INC280 and buparlisib (BKM120), as well as the anti-tumor activity of the combination, in patients with recurrent glioblastoma with PTEN mutations, homozygous deletion of PTEN or PTEN negative by IHC. In addition, the anti-tumor activity of INC280 single agent should have been assessed in patients with recurrent glioblastoma with c-Met alteration.

Detailed description:
This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD and/or to identify the recommended phase II dose (RP2D) for the combination of INC280 and buparlisib, followed by the phase II part to assess the clinical efficacy of INC280 single agent and in combination with buparlisib (BKM120), and to further assess the safety of the combination. In addition, a surgical arm should have started concurrently with the phase II part, to determine the PK/PD profile of the study drug combination in patients undergoing tumor resection for recurrent glioblastoma after 7 to 10-days treatment.

RP2D was not declared due to a lack of efficacy of the combination in the phase Ib stage, and phase II was continued with INC280 monotherapy only.

Arms:
arm 1: To estimate the safe dose of the combination INC280 and buparlisib arm 2: To estimate anti-tumor efficacy of INC280 single agent and in combination with buparlisib

Interventions: intervention 1: INC280 intervention 2: Buparlisib
Intervention descriptions: intervention 1: Phase Ib: INC280 was given at the starting dose of 200mg capsules twice daily with escalation to higher strengths.

Phase II: INC280 was given at the dose of 400mg (tablets) twice daily. intervention 2: Buparlisib was given at the starting dose of 50mg once daily with escalation to higher strengths.

Protocol document: