A Phase 2 Trial of Ponatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor

A Phase 2 Trial of Ponatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor

Gastrointestinal Stromal Tumor

Completed

2

Start Date 05/29/2013

Age of Trial (yrs) 11.5

Gleevec-resistant

KIT/PDGFRA inhibitor+ VEGF inhibitor (TKI)

Block related tumor signal paths

Specifically GIST and only GIST

AP24534-12-202

Ariad Pharmaceuticals

Contact: Frank G. Haluska, MD, PhD Contact: Christopher D. Turner, MD

frank.haluska@ariad.com christopher.turner@ariad.com

617-494-0400

Oral

NOTE: On October 31th, 2013, the FDA moved to stop commercial distribution of ponatiniib because of safety concerns including blood clots and other vascular events. GIST patients that we in the trial as of that date are continuing to receive ponatinib, but no new patients are being accepted. See links for details.
This is a non-randomized, open label, multicenter phase 2 study to evaluate the efficacy and safety of ponatinib in patients with metastatic and/or unresectable GIST after prior failure of at least 1 TKI. Patients whose tumors have an activating mutation in exon 11 of cellular KIT (KIT) will be enrolled into Cohort A. Patients whose tumors have other activating mutations will be enrolled into in Cohort B.

The primary objective is to assess clinical benefit in patients with KIT exon 11-mutant GIST (Cohort A) defined as clinical benefit rate (CBR), which is the composite of complete response (CR), partial response (PR) and stable disease (SD) lasting ≥16 weeks per modified response evaluation criteria in solid tumors (RECIST 1.1 [Demetri et al., 2012]) as a measure of disease control. The secondary objective is to assess clinical benefit in patients with GIST that lacks an activating KIT exon 11 mutation (Cohort B) and in the total patient population. The efficacy assessments are tumor response using Response Criteria in Solid Tumors (RECIST) Version 1.1, modified for GIST and assessment of progression-free survival (PFS) and overall survival (OS). The safety assessments include routine physical and laboratory evaluations, electrocardiogram (ECG), echocardiograms (ECHO), and adverse event (AE) monitoring. Other assessments include optional 18F fluorodeoxyglucose positron emission tomography (FDG-PET); optional pre- and post-treatment tumor biopsy for pharmacodynamic studies; and pharmacokinetics (PK). It is estimated that accrual will be complete within 1 year; the total estimated duration of the study is 3 years.