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

Arog Pharmaceuticals

Status and phase

Completed

Phase 2

Conditions

D842-related Mutant GIST

Treatments

Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID

Study type

Interventional

Funder types

Industry

Identifiers

NCT01243346

ARO-BRE-002

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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