Pilot Study of PLX3397 in Patients With Advanced Castration-Resistant Prostate Cancer (CRPC)

Study Overview
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Brief Summary
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The main objective of this study is to evaluate the effects of PLX3397 on male subjects with CRPC. Secondary objectives include evaluating the safety and tolerability of PLX3397 and the anti-tumor effects that PLX3397 has on the the subjects.

Official Title
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A Pilot Study of PLX3397 in Advanced Castration-Resistant Prostate Cancer (CRPC) Patients With Bone Metastasis and High Circulating Tumor Cell (CTC) Counts

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: PLX3397


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed prostate cancer, currently with objective progressive disease. Castrate level of testosterone (<50 ng/dL). Baseline circulating tumor cell (CTC) count ≥10/7.5 mL blood. Archival tumor tissue (unstained sections, paraffin block, or frozen tumor tissue) has been requisitioned for shipment to the central laboratory. Karnofsky performance status of 80-100. Adequate organ and marrow function. Exclusion Criteria: The subject has received: Any systemic chemotherapy (including investigational agents) within 4 weeks (with the exception of nitrosoureas/mitomycin C within 6 weeks), of the first dose of study treatment, OR Biological agents (antibodies, immune modulators, cytokines, or vaccines) within 6 weeks of the first dose of study treatment, OR Hormonal anticancer therapy (not including LHRH agonists or antagonists) within 2 weeks before the first dose of study treatment. Specific restrictions on prior hormonal and other anticancer treatments are detailed in inclusion criterion, OR Small-molecular kinase inhibitors or any other type of investigational agent within 4 weeks before the first dose of study treatment or 5 half-lives of the compound or active metabolite, whichever is shorter. The subject has received drugs used to control loss of bone mass (e.g., bisphosphonates) within 4 weeks prior to the first dose of study treatment. The subject has symptomatic or uncontrolled brain metastasis or epidural disease requiring current treatment including steroids and anti-convulsants. The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) >450 ms at screening. The subject has uncontrolled or significant intercurrent illness including, but not limited to, the following conditions: Cardiovascular disorders such as symptomatic congestive heart failure (CHF), *Uncontrolled hypertension Unstable angina pectoris, clinically-significant cardiac arrhythmias History of stroke (including transient ischemic attack [TIA] or other ischemic event) within 6 months of study treatment Myocardial infarction within 6 months of study treatment History of thromboembolic event requiring therapeutic anticoagulation within 6 months of study treatment or main portal vein or vena cava thrombosis or occlusion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLX3397<br>Participants will take daily oral dose of PLX3397 for 28 day cycles. Participants will continue to take PLX3397 until disease progression or toxicity. | Drug: PLX3397<br>* Capsules administered twice daily, continuous dosing. Subjects will take PLX3397 at 1000 mg/day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of High Circulating Tumor Cell Count Number In Men With Radiographically Progressive Castration-Resistant Prostate Cancer and High Circulating Tumor Cells | Effects of PLX3397 on CTC number in men with radiographically progressive CRPC and high CTC counts (≥10 CTCs/7.5 mL of blood using CellSearch Assay) CTC counts were to be evaluated at the following time points: Screening, Baseline, every 4 weeks after treatment initiation, and at Safety Follow-up. Radiographic tumor evaluation were to be performed every 8 weeks. Progression at the first reassessment required a confirmatory scan at a minimum of 6 weeks later, and treatment with study medication was to continue until the progression had been confirmed. | See measure description for time frame. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Treatment-Related Adverse Events by System Organ Class and Preferred Term |  | Assessed from first dose through at least 4 weeks after the last dose. | 
| Number of Participants Reporting Treatment-Emergent Adverse Events by Worst Severity Grade | Adverse events (AEs) were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0, where 1=mild, 2=moderate, 3=severe, 4=life-threatening, and 5=death related to AE. | Assessed from first dose through at least 4 weeks after the last dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRPC, Prostate Cancer, Bone metastasis, Advanced Castration-Resistant Prostate Cancer (CRPC)