Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 as a Single Agent and In Combination With Enzalutamide in Participants With Metastatic Castrate-Resistant Prostate Cancer

Overview

About this study

This study consists of two phases: Dose Escalation (Phase 1b) and Dose Expansion (Phase 2) The Dose Escalation phase will evaluate the safety and tolerability of GS-5829 as a single agent and in combination with enzalutamide, as well as determine the maximum tolerated dose (MTD) of GS-5829 as a single agent and in combination with enzalutamide in participants with metastatic castrate-resistant prostate cancer (mCRPC). The Dose Expansion phase will evaluate the following: - In group 1, the efficacy of GS-5829 as a single agent in participants with mCRPC who have progressed while receiving enzalutamide (may have also received abiraterone) - In group 2, the efficacy of GS-5829 combined with enzalutamide in participants with mCRPC who have progressed while receiving treatment with abiraterone (may not have previously received enzalutamide) - In group 3, the efficacy of GS-5829 combined with enzalutamide in participants with mCRPC who have had Prostate Specific Antigen (PSA) progression, but not radiographic progression, while receiving treatment with enzalutamide (participants may have also previously received abiraterone)

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Key Inclusion Criteria:

  • Histologically or cytologically confirmed prostate cancer (individuals with primary neuroendocrine carcinoma of prostate are excluded)
  • Must have documented progressive disease by meeting at least one of the Prostate Cancer Working Group 2 Criteria
  • Castration resistant disease defined as ongoing androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy and serum testosterone level ≤ 1.73 nmol/l (50 ng/dL) at screening visit. Individuals who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial.
  • Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by CT/MRI. Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  • Adequate organ function defined as follows:
    • Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without platelet transfusion or any growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit)
    • Hepatic: Aspartate transaminase (AST) / Alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); Total or conjugated bilirubin ≤ 1.5 x ULN
    • Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockroft-Gault method
  • Coagulation: International Normalized Ratio (INR) ≤ 1.2

Key Exclusion Criteria:

  • Known brain metastasis or leptomeningeal disease
  • Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of Cycle 1 Day 1
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of GS-5829, including any unresolved nausea, vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1
  • Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 21 days or 5 half-lives, whichever is longer, of study drug dosing (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); concurrent use of an luteinizing hormone releasing hormone (LHRH) agonist is permitted for all individuals and ongoing enzalutamide is required in Group 3.
  • History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms).
  • Prior exposure to bromodomain (BET) inhibitors
  • Clinically significant bleeding within 28 days of Cycle 1 Day 1
  • Known human immunodeficiency virus (HIV) infection
  • HBsAg positive
  • Hepatitis C virus (HCV) antibody positive
  • Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or moderate/strong CYP3A4 inducers within 2 weeks prior to the first dose of study drug (with the exception of enzalutamide in the combination arms)
  • Evidence of bleeding diathesis
  • History of hemoptysis of ≥ 2.5 mL/1 teaspoon within 6 months of Cycle 1 Day 1
  • History of high grade esophageal or gastric varices
  • Anticoagulation/antiplatelet therapy within 7 days of Cycle 1 Day 1, including low molecular weight heparin, or warfarin.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Alan Bryce, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
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CLS-20264710

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