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

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: PLX3397

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PLX3397; 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; Capsules administered twice daily, continuous dosing. Subjects will take PLX3397 at 1000 mg/day.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: Plexxikon

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2012
• Primary Completion (Actual): March 11, 2013
• Study Completion (Actual): March 11, 2013

Study Registration Dates

• First Submitted: December 20, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 26, 2011

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Prostate Cancer; CRPC; Bone metastasis; Advanced Castration-Resistant Prostate Cancer (CRPC)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PLX108-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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/
• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR