Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blinded, placebo-controlled, trial of oral crenolanib versus oral placebo in combination with best supportive care in subjects with advanced or metastatic GIST with a D842V mutation in the PDGFRA gene. Approximately 120 subjects will be randomized in a 2:1 ratio to receive either crenolanib 100 mg or matching placebo orally (PO) 3 times daily (TID) in combination with best supportive care.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Crenolanib in Subjects With Advanced or Metastatic Gastrointestinal Stromal Tumors With a D842V Mutation in the PDGFRA Gene

Conditions
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GIST With D842V Mutated PDGFRA Gene

Intervention / Treatment
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* Drug: Crenolanib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically-confirmed advanced or metastatic GIST with a D842V mutation in the PDGFRA gene as determined by central laboratory testing Measurable disease as per modified RECIST 1.1 • A lesion in an area that was previously treated with local therapy (e.g. radiation, surgery, or cryotherapy) can be considered measurable disease as long as there is objective evidence of progression of the lesion prior to randomization Subjects (male or female) ≥ 18 years of age Female subjects with reproductive potential must have negative serum or urine pregnancy test Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Exclusion Criteria: Severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis) Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) Female subject who is pregnant or breastfeeding, or planning to become pregnant within 30 days after ending treatment Systemic anti-cancer treatment (e.g. chemotherapy, tyrosine kinase inhibitors, immunotherapy, or investigational agents) or investigational device within 3 weeks or 5 half-lives (if the drug's half-life in subject is known) prior to randomization, whichever is shorter

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crenolanib Arm<br>Investigational product (crenolanib) | Drug: Crenolanib<br> <br> * Other names: Crenolanib Besylate;|
| Placebo Comparator: Placebo Arm<br>Matching placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) will be measured from the date of randomization to the date of the first objective radiological disease progression according to centralized committee assessment using modified RECIST version 1.1 or death. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) will be measured from the date of randomization to the date of death from any cause. OS will be estimated using the Kaplan-Meier method. |  | 3 years |