This is a multi-center, first-in-human, open-label, Phase 1/2A dose-escalation study in which eligible patients with metastatic castration-resistant prostate carcinoma (mCRPC) will receive oral doses of TRC253. The study will be conducted in 2 parts: part 1 (dose escalation) and part 2 (dose expansion).
Name: TRC253
Description: The recommended phase 2 dose of TRC253 will be determined.
Measure: Recommended Phase 2 dose (RP2D) of TRC253 Time: 8 monthsDescription: Safety assessments will be based on medical review of adverse event reports and the results of clinical laboratory tests, electrocardiograms, vital sign measurements, and physical examinations.
Measure: Safety profile of TRC253 including adverse events assessed by CTCAE v4.03 Time: 18 monthsDescription: PSA response at Week 12 will be evaluated according to PCWG3 criteria.
Measure: Serum prostate-specific antigen (PSA) response at Week 12 according to Prostate Cancer Working Group (PCWG3) criteria Time: 3 monthsDescription: Mean change in QTcF at Cmax
Measure: Exposure-QTcF relationship: mean change in QTcF at Cmax Time: 18 monthsDescription: To confirm the RP2D, patients at select dose levels will undergo PET scans using FDHT, a radiopharmaceutical specifically designed to image binding to AR.
Measure: Extent of receptor occupancy by FDHT-PET scan Time: 18 monthsDescription: Time to PSA progression, and radiographic PFS.
Measure: Preliminary anti-tumor effects of TRC253: time to PSA progression and radiographic PFS according to PCWG3 Time: 18 monthsDescription: CTC enumeration and molecular characterization of a panel of markers including AR-V7.
Measure: Resistance markers assessed from circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) Time: 18 monthsAllocation: N/A
Single Group Assignment
There is one SNP
Patients will be centrally screened for the presence of the AR F876L (androgen receptor F876L) mutation from a plasma sample and enrolled into Cohort 1 (AR F876L positive) or Cohort 2 (AR F876L negative). --- F876L ---
Patients will be centrally screened for the presence of the AR F876L (androgen receptor F876L) mutation from a plasma sample and enrolled into Cohort 1 (AR F876L positive) or Cohort 2 (AR F876L negative). --- F876L --- --- F876L ---
Patients will be centrally screened for the presence of the AR F876L (androgen receptor F876L) mutation from a plasma sample and enrolled into Cohort 1 (AR F876L positive) or Cohort 2 (AR F876L negative). --- F876L --- --- F876L --- --- F876L ---
Patients will be centrally screened for the presence of the AR F876L (androgen receptor F876L) mutation from a plasma sample and enrolled into Cohort 1 (AR F876L positive) or Cohort 2 (AR F876L negative). --- F876L --- --- F876L --- --- F876L --- --- F876L ---