Phase II Study of Crenolanib (CP-868,596), for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions in the PDGFRA Gene
|D842-related Mutant GIST||Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions, Including the D842V Mutation, in the PDGFRA Gene|
- The primary end-point is overall response rate [ Time Frame: 1.5 years ]To determine the response rate of patients with advanced D842V mutant GIST, when treated with Crenolanib (CP-868,596). Response will primarily be determined by RECIST criteria
- Progression free survival rate [ Time Frame: 6 months ]To determine the progression free survival rate at 6 months in patients with advanced GIST with the D842V mutation in the PDGFRA gene, when treated with CP-868,596 (crenolanib).
- Obtain toxicity information [ Time Frame: 1 year ]To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
- PKPD analysis [ Time Frame: 1 year ]To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
|Study Start Date:||April 2011|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
|Experimental: Crenolanib (CP-868,596)||
Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
Highly potent inhibitor of both PDGFR receptors alpha and beta
Crenolanib (CP-868,596) is an orally bioavailable, selective inhibitor of PDGFR receptor tyrosine kinase with IC50s of 0.4 ng/mL and 0.8 ng/mL for PDGFRα and PDGFRβ, respectively.
In preclinical models of cell lines with the D842V mutation in the PDGFRA gene, crenolanib (CP-868,596) blocked phosphorylation of PDGFRα at nanomolar concentrations, suggesting that it may provide a clinical benefit to patients with D842V mutant GIST.
In addition, crenolanib was also active in inhibiting phosphorylation of cell lines with two point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01243346
|United States, Oregon|
|Knight Cancer Institute, Oregon Health and Science University|
|Portland, Oregon, United States, 97239-3098|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|Principal Investigator:||Margaret von Mehren, MD||Fox Chase Cancer Center|
|Principal Investigator:||Michael C Heinrich, MD||OHSU Knight Cancer Institute|