Study of Crenolanib for the Treatment of Patients With Advanced GIST With the D842-related Mutations and Deletions in the PDGFRA Gene

Phase 2

Completed

• Conditions: D842-related Mutant GIST

• Registration Number: NCT01243346
• Lead Sponsor: Arog Pharmaceuticals, Inc.

Brief Summary

This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib (CP-868,596) in patients with D842-related mutant metastatic GIST.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2010-11-17
• Study First Submitted QC: 2010-11-17
• Study First Posted: 2010-11-18
• Study Start: 2011-04
• Primary Completion: 2014-07
• Study Completion: 2014-07
• Status Verified: 2018-06
• Disposition First Submitted: 2018-06-26
• Disposition First Submitted QC: 2018-06-26
• Last Update Submitted: 2018-06-26
• Disposition First Posted: 2018-06-28
• Last Update Posted: 2018-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
The primary end-point is overall response rate	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

Secondary Outcome Measures

Name	Time	Method
Progression free survival rate	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	1 year	To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
PKPD analysis	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.

Trial Locations

Locations (2)

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Knight Cancer Institute, Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States