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Report for Clinical Trial NCT02987829

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

An Open-label Phase 1/2A Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of TRC253, an Androgen Receptor Antagonist, in Patients With Metastatic Castration-resistant Prostate Cancer

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).

NCT02987829 Metastatic Castrate-resistant Prostate Cancer Adenocarcinoma, Prostate
MeSH:Prostatic Neoplasms Adenocarcinoma
HPO:Prostate cancer Prostate neoplasm

1 Interventions

Name: TRC253

Description: TRC253 is a high-affinity, small molecule antagonist of the androgen receptor (AR) with inhibitory activity against wild type AR and specific mutated variants of AR. TRC253 blocks AR nuclear translocation as well as AR binding to DNA and is an antagonist of transcription for wild type AR and mutated AR. TRC253 is orally active and does not have agonist activity towards either the wild type or mutated ARs. TRC253 treatment in the Hershberger assay results in complete inhibition of androgen sensitive organ development. TRC253 is efficacious in an LNCaP xenograft model driven by F876L (also known as F877L) mutant AR.
Type: Drug
Group Labels: 1

TRC253


Primary Outcomes

Description: The recommended phase 2 dose of TRC253 will be determined.

Measure: Recommended Phase 2 dose (RP2D) of TRC253

Time: 8 months

Secondary Outcomes

Description: 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 months

Description: 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 months

Description: Mean change in QTcF at Cmax

Measure: Exposure-QTcF relationship: mean change in QTcF at Cmax

Time: 18 months

Description: 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 months

Description: 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 months

Other Outcomes

Description: 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 months

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 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 ---

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 ---



HPO Nodes


HPO: