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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 currently recruiting participants.
Verified January 2012 by Arog Pharmaceuticals LLC

First Received on November 17, 2010.   Last Updated on January 10, 2012   History of Changes
Sponsor: Arog Pharmaceuticals LLC
Information provided by: Arog Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01243346
  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) 340mg
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


Estimated Enrollment: 20
Study Start Date: April 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Crenolanib (CP-868,596) Drug: Crenolanib besylate (CP-868,596-26) 340mg
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 may have received prior chemotherapy or radiation therapy. Patients must have recovered from any prior therapy and at least 4 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 within 4 weeks of start of study drug
  • 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 on proton pump inhibitors
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01243346

Contacts
Contact: Haley Marshall 214-593-0508 hmarshall@arogpharma.com
Contact: Abhijit Ramachandran, M.S. 214-593-0515 aramachandran@arogpharma.com

Locations
United States, Oregon
Knight Cancer Institute, Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Tracy Walker, RN, BSN         walkertr@ohsu.edu    
Contact: Hotline     503-494-1080        
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Kathleen Lear, RN, OCN, CCRP     215-214-1511     Kathleen.Lear@fccc.edu    
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:
No publications provided

Responsible Party: Hemanshu Shah / Chief Operating Officer, 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: January 10, 2012
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
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases

ClinicalTrials.gov processed this record on May 23, 2012