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

Primary Purpose

D842-related Mutant GIST

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
Sponsored by
Arog Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for D842-related Mutant GIST focused on measuring Gastrointestinal Stromal Tumor, PDGFR Inhibitor, Crenolanib (CP-868,596)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • Male or female, of any racial or ethnic group
  • Age 18 years or older
  • Life expectancy of greater than 12 weeks
  • Patient able and willing to provide informed consent
  • Normal liver function, defined as AST and ALT ≤2.5x ULN, and Total Bilirubin ≤ 2x ULN.
  • Total creatinine ≤ 1.5x ULN
  • ECOG Performance Status 0 - 2 (Appendix II)
  • Patients must have histologically or cytologically confirmed GIST with a D842-related mutation or deletion on the PDGFRA gene
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10.1.2 for the evaluation of measurable disease.
  • Patients must have recovered from any prior therapy and completed the minimum of, either 5 half-lives of prior therapy or 2 weeks must have elapsed since prior treatment

Exclusion Criteria

  • Patient unable to provide informed consent
  • ECOG Performance status > 2
  • Any concurrent anticancer therapy, immunotherapy, or hormonal therapy.
  • Any other investigational agents taken within 2 weeks of start of study drug or if study drug will commence within 5 half-lives of prior therapy
  • Patients with known or active Hepatitis B or C; liver cirrhosis.
  • Patients with active fungal, viral, and bacterial infections
  • Positive serum pregnancy test
  • Pregnant or lactating women
  • Patients on concomitant medications that induce or inhibit CYP3A4 (Appendix III)
  • Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs

Sites / Locations

  • Knight Cancer Institute, Oregon Health and Science University
  • Fox Chase Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Crenolanib (CP-868,596)

Arm Description

Outcomes

Primary Outcome Measures

The primary end-point is overall response rate
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

Progression free survival rate
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
To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
PKPD analysis
To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.

Full Information

First Posted
November 17, 2010
Last Updated
June 26, 2018
Sponsor
Arog Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01243346
Brief Title
Study of Crenolanib for the Treatment of Patients With Advanced GIST With the D842-related Mutations and Deletions in the PDGFRA Gene
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arog Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
D842-related Mutant GIST
Keywords
Gastrointestinal Stromal Tumor, PDGFR Inhibitor, Crenolanib (CP-868,596)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Crenolanib (CP-868,596)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
Intervention Description
Highly potent inhibitor of both PDGFR receptors alpha and beta
Primary Outcome Measure Information:
Title
The primary end-point is overall response rate
Description
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
Time Frame
1.5 years
Secondary Outcome Measure Information:
Title
Progression free survival rate
Description
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).
Time Frame
6 months
Title
Obtain toxicity information
Description
To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
Time Frame
1 year
Title
PKPD analysis
Description
To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Male or female, of any racial or ethnic group Age 18 years or older Life expectancy of greater than 12 weeks Patient able and willing to provide informed consent Normal liver function, defined as AST and ALT ≤2.5x ULN, and Total Bilirubin ≤ 2x ULN. Total creatinine ≤ 1.5x ULN ECOG Performance Status 0 - 2 (Appendix II) Patients must have histologically or cytologically confirmed GIST with a D842-related mutation or deletion on the PDGFRA gene Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10.1.2 for the evaluation of measurable disease. Patients must have recovered from any prior therapy and completed the minimum of, either 5 half-lives of prior therapy or 2 weeks must have elapsed since prior treatment Exclusion Criteria Patient unable to provide informed consent ECOG Performance status > 2 Any concurrent anticancer therapy, immunotherapy, or hormonal therapy. Any other investigational agents taken within 2 weeks of start of study drug or if study drug will commence within 5 half-lives of prior therapy Patients with known or active Hepatitis B or C; liver cirrhosis. Patients with active fungal, viral, and bacterial infections Positive serum pregnancy test Pregnant or lactating women Patients on concomitant medications that induce or inhibit CYP3A4 (Appendix III) Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret von Mehren, MD
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael C Heinrich, MD
Organizational Affiliation
OHSU Knight Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Knight Cancer Institute, Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22745105
Citation
Heinrich MC, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res. 2012 Aug 15;18(16):4375-84. doi: 10.1158/1078-0432.CCR-12-0625. Epub 2012 Jun 27.
Results Reference
background
Links:
URL
http://www.fccc.edu
Description
Fox Chase Cancer Center
URL
http://www.arogpharma.com
Description
AROG Pharmaceuticals, LLC, is dedicated to the scientific development of novel anticancer drugs for niche indications
URL
http://www.ohsu.edu/xd/health/services/cancer/
Description
OHSU Knight Cancer Institute
URL
http://meetinglibrary.asco.org/content/170566-176
Description
Poster Discussion Session, Sarcoma, 2016 ASCO Annual Meeting

Learn more about this trial

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

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