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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

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ClinicalTrials.gov Identifier: NCT01243346
Recruitment Status : Completed
First Posted : November 18, 2010
Last Update Posted : June 28, 2018
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE November 17, 2010
First Posted Date  ICMJE November 18, 2010
Last Update Posted Date June 28, 2018
Study Start Date  ICMJE April 2011
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2011)
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 17, 2010)
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 CP-868,596. Response will primarily be determined by RECIST criteria
Change History Complete list of historical versions of study NCT01243346 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2013)
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Crenolanib for the Treatment of Patients With Advanced GIST With the D842-related Mutations and Deletions in the PDGFRA Gene
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE D842-related Mutant GIST
Intervention  ICMJE Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
Highly potent inhibitor of both PDGFR receptors alpha and beta
Study Arms  ICMJE Experimental: Crenolanib (CP-868,596)
Intervention: Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2012)
20
Original Estimated Enrollment  ICMJE
 (submitted: November 17, 2010)
10
Actual Study Completion Date  ICMJE July 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01243346
Other Study ID Numbers  ICMJE ARO-BRE-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Arog Pharmaceuticals, Inc.
Study Sponsor  ICMJE Arog Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Margaret von Mehren, MD Fox Chase Cancer Center
Principal Investigator: Michael C Heinrich, MD OHSU Knight Cancer Institute
PRS Account Arog Pharmaceuticals, Inc.
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP