Dose Escalation and Dose Expansion Study of GSK525762 in Combination With Androgen Deprivation Therapy and Other Agents in Subjects With Castrate-resistant Prostate Cancer

Official Title

A Phase IB Open-label, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Combination With Androgen Deprivation Therapy and Other Agents in Subjects With Castrate-resistant Prostate Cancer (CRPC)

Summary:

The study aims to evaluate the combination of GSK525762 with other agents that have been shown to be effective in the treatment of CRPC or metastatic CRPC, including approved agents (e.g., abiraterone, enzalutamide) as well as investigational agents for mCRPC that have proven to show efficacy and can be combined based on complimentary mechanism of action. As a first step, the combination of GSK525762 will be evaluated as a combination with abiraterone or enzalutamide in men with metastatic or advanced castrate-resistant prostate cancer who have progressed on at least one line of prior androgen receptor (AR)-targeted therapy. This study is designed to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) based on safety, tolerability, pharmacokinetic, and efficacy profiles of GSK525762 in combination with either abiraterone (Arm A) or enzalutamide (Arm B). Arm A and Arm B will further have 2 cohorts: A1, A2 and B1, B2 respectively based on prior lines of therapy (L2 [chemo-naive subjects treated with a second androgen-deprivation therapy] and Lx [subjects treated with both prior androgen-deprivation therapy and chemotherapy]). During dose escalation, both the treatment arms (A and B) will follow a modified Toxicity Probability Interval (mTPI) design. Approximately 130 subjects will be enrolled worldwide in this study. Subjects from both dose escalation and dose expansion may be combined to reach 30 subjects. The total duration of study will be approximately 2 to 3 years. A subject will be considered to have completed the study if they are followed until death.

Trial Description

Primary Outcome:

  • Number of subjects with adverse events (AE) and serious adverse events (SAE)
  • Number of subjects with dose reductions or delays
  • Number of subjects withdrawn due to toxicity
  • Number of subjects with abnormality in laboratory parameters
  • Number of subjects with abnormality in vital signs
  • Number of subjects with abnormality in electrocardiogram (ECG)
  • Number of subjects with abnormality in any cardiotoxicity parameters
  • Number of subjects with abnormality in gastrointestinal parameters
  • Percentage of subjects with Prostate Specific Antigen 50 (PSA50)
Secondary Outcome:
  • Plasma concentration of GSK525762 and selected metabolites
  • Plasma concentration of abiraterone or enzalutamide
  • Overall response rate (ORR) based on Prostate Cancer Working Group (PCWG3)-modified Response Evaluation Criteria In Solid Tumours (RECIST) 1.1
  • Circulating Tumour Cell (CTC) response
  • Percentage of subjects with PSA response at Week 4
  • Time to disease progression
  • Radiographic Progression-free survival (rPFS) based on PCWG3-modified RECIST 1.1
  • Composite Response Rate defined as any one of the following: a) Response based on PCWG3-modified RECIST1.1, b) PSA decrease of ≥50% at Week 12 and thereafter, or c) Circulating Tumour-cell Count Conversion
  • The performance status as measured by Eastern Cooperative Oncology Group (ECOG) scale
  • The change in the quality of life as measured by European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30)
  • Pain as assessed with The Brief Pain Inventory-Short Form (BPI-SF)

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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