D842-related Mutant GIST Clinical Trial
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
| NCT number | NCT01243346 |
| Other study ID # | ARO-BRE-002 |
| Secondary ID | |
| Status | Completed |
| Phase | Phase 2 |
| First received | |
| Last updated | |
| Start date | April 2011 |
| Est. completion date | July 2014 |
| Verified date | June 2018 |
| Source | Arog Pharmaceuticals, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | July 2014 |
| Est. primary completion date | July 2014 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | Knight Cancer Institute, Oregon Health and Science University | Portland | Oregon |
| Lead Sponsor | Collaborator |
|---|---|
| Arog Pharmaceuticals, Inc. |
United States,
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The primary end-point is overall response rate | 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 | 1.5 years | |
| Secondary | Progression free survival rate | 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). | 6 months | |
| Secondary | Obtain toxicity information | To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene. | 1 year | |
| Secondary | PKPD analysis | To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene. | 1 year |