SNPMiner Trials (Home Page)
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 yearSecondary Outcomes
Description: Among mCRPC patients receiving abiraterone acetate and enzalutamide
Measure: Potential biomarkers that are associated with treatment efficacy and/ or resistance Time: 1 yearOther Outcomes
Measure: PSA response rate in mCRPC patients treated with first-line abiraterone acetate or enzalutamide Time: 1 year2 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
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 monthsSecondary 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 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 monthsOther 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