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
  Purpose

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.


Condition Intervention Phase
D842-related Mutant GIST
Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Arog Pharmaceuticals LLC:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 20
Study Start Date: April 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01243346

Locations
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
Sponsors and Collaborators
Arog Pharmaceuticals LLC
Investigators
Principal Investigator: Margaret von Mehren, MD Fox Chase Cancer Center
Principal Investigator: Michael C Heinrich, MD OHSU Knight Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Arog Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01243346     History of Changes
Other Study ID Numbers: ARO-BRE-002
Study First Received: November 17, 2010
Last Updated: December 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Arog Pharmaceuticals LLC:
Gastrointestinal Stromal Tumor
PDGFR Inhibitor
Crenolanib (CP-868,596)

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Crenolanib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014