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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT01243346
First received: November 17, 2010
Last updated: December 31, 2013
Last verified: December 2013

November 17, 2010
December 31, 2013
April 2011
August 2014   (final data collection date for primary outcome measure)
The primary end-point is overall response rate [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
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
The primary end-point is overall response rate [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
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
Complete list of historical versions of study NCT01243346 on ClinicalTrials.gov Archive Site
  • Progression free survival rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
  • PKPD analysis [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
Not Provided
Not Provided
Not Provided
 
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
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

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
D842-related Mutant GIST
Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
Highly potent inhibitor of both PDGFR receptors alpha and beta
Experimental: Crenolanib (CP-868,596)
Intervention: Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
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. Epub 2012 Jun 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20
September 2014
August 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01243346
ARO-BRE-002
No
Arog Pharmaceuticals LLC
Arog Pharmaceuticals LLC
Not Provided
Principal Investigator: Margaret von Mehren, MD Fox Chase Cancer Center
Principal Investigator: Michael C Heinrich, MD OHSU Knight Cancer Institute
Arog Pharmaceuticals LLC
December 2013

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