Phase 2 Trial of Ponatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor Following Failure of Prior Therapy With at Least 1 Tyrosine Kinase Inhibitor
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.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical Benefit Rate (CBR)
To assess clinical benefit rate in patients with KIT exon 11-mutant GIST. Defined as the composite of complete response (CR), partial response (PR), and stable disease (SD) lasting ≥16 weeks per modified RECIST 1.1 as a measure of disease control
16 weeks after first dose
No
United States: Food and Drug Administration
AP24534-12-202
NCT01874665
May 2013
Name | Location |
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Oregon Health & Sciences University | Portland, Oregon 97201 |