MedicalResearch.com Interview with: Nicholas J. Vogelzang, MD, FASCO, FACP Medical Oncologist at Comprehensive Cancer Centers of Nevada Associate Chair, US Oncology Research Genitourinary Committee  MedicalResearch.com: What is the background for this study? Response: According to the American Cancer Society, prostate cancer is the second leading cause of cancer death in men in the U.S. New approaches are needed to target the androgen receptor (AR), a critical driver of metastatic castration resistant prostate cancer (mCRPC). Current agents work by decreasing androgen levels (abiraterone) or blocking androgen binding to AR (enzalutamide). Despite rapid and dramatic responses to standards of care, all patients with metastatic disease progress to the castration resistant state and their tumors continue to be dependent on the AR signaling axis.¹ Study design:

• “3 + 3” dose escalation; starting dose = 35 mg, orally, once daily with food
• Dose increases dependent on toxicities
  • Range 25% to 100% based on severity of AEs

Inclusion criteria:

• Men with mCRPC, regardless of AR status
• At least two prior systemic therapies, at least one of which was abiraterone or enzalutamide
• Disease progression on most recent therapy
  • Rising PSA or 2+ new lesions upon bone scan

Endpoints:

• Primary:
  • Define the maximum tolerated dose and recommended phase 2 dose
• Secondary:
  • Pharmacokinetics
  • Anti‐tumor activity (PSA50, RECIST criteria)
• Exploratory:
  • Biomarkers
    • ctDNA mutational profiling
    • AR levels in optional paired biopsies
    • AR and AR‐ V7 levels in circulating tumor cells (CTCs) 

(more…)