A Dose-finding Study of a Combination of Imatinib and BKM120 in the Treatment of 3rd Line GIST Patients

A Dose-finding Study of a Combination of Imatinib and BKM120 in the Treatment of 3rd Line GIST Patients

Gastrointestinal Stromal Tumor

Completed

1

Start Date 04/01/2012

Age of Trial (yrs) 12.6

Gleevec-resistant

KIT/PDGFRA + PI3K Inhibitor

Block KIT + Block related tumor signal paths

Specifically GIST and only GIST

CSTI571X2101

Novartis Pharmaceuticals

Contact: Novartis Pharmaceutical 1-888-669-6682

Oral

PI3K has been shown to be an important signaling protein that is downstream from KIT. Lab experiments suggest that inhibiting KIT and PI3K at the same time may be effective and that the effect may even persist for some time after stopping the combination.
This is a phase 1 trial designed to look at dose and safety. A secondary endpoint will be to examine preliminary efficacy measured as benefit lasting at least 16 weeks.
Experimental: STI571 (imatinib mesylate) and BKM120
The study will comprise of 2 parts. A dose escalation and a dose expansion part. Patients will receive increasing doses of BKM120 (40, 60, 80, 100 mg) in combination with 400mg imatinib daily until maximum tolerated dose (MTD) and rapid phase 2 dose (RP2D) is determined. 35 patients will enter the expansion phase with 18 patients having a pharmacokintic (PK) run-in period of 8 days receiving imatinib monotherapy or BKM120 monotherapy.
Patients may receive either imatinib or BKM120 first for 8 days followed by adding the other drug.