SNPMiner Trials by Shray Alag


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Report for Mutation F876L

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials


1 A Randomized Phase II Study of Sequencing Abiraterone Acetate and Enzalutamide in Metastatic Castration-Resistant Prostate Cancer

This study is being offered to patients who have castrate-resistant (also known as hormone-refractory) prostate cancer. The cancer has metastasized or spread outside the prostate area to other parts of the body. The purpose of this study is to evaluate the effects of sequencing hormonal therapies (abiraterone acetate and enzalutamide) and to assess treatment efficacy of these two agents.

NCT02125357 Metastatic Castration-Resistant Prostate Cancer Drug: Abiraterone acetate Drug: Enzalutamide
MeSH:Prostatic Neoplasms
HPO:Prostate cancer Prostate neoplasm

In pre-clinical studies, other potential mechanisms of resistance to these agents include increased expression of AR splice variants (abiraterone and enzalutamide) increased expression of CYP17 (abiraterone), upregulation of the stress-activated chaperone protein clusterin (enzalutamide only) and a point mutation (F876L) in the ligand-binding domain of the AR (enzalutamide only). --- F876L ---

Primary Outcomes

Measure: PSA response rate in mCRPC patients with PSA progression on first-line therapy when crossed over to second-line therapy with the opposite agent

Time: 1 year

Secondary Outcomes

Description: Among mCRPC patients receiving abiraterone acetate and enzalutamide

Measure: Potential biomarkers that are associated with treatment efficacy and/ or resistance

Time: 1 year

Other Outcomes

Measure: PSA response rate in mCRPC patients treated with first-line abiraterone acetate or enzalutamide

Time: 1 year

2 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 Drug: TRC253
MeSH:Prostatic Neoplasms Adenocarcinoma
HPO:Prostate cancer Prostate neoplasm

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 ---

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


HPO Nodes