Business decision.

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.

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.

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Adverse events were collected from after first dose to 28 days after last dose.

Adverse events that emerge (or worsen) from after the first dose of study drug and within 28 days after last dose.

This study did not meet its planned enrollment goal of 20 participants by the end of 2012. Therefore, enrollment was terminated and efficacy was not evaluated; only the safety results are reported.