Phase 1 - study of GSK2636771 plus Enzalutamide in mCRProstate Cancer
Research type
Research Study
Full title
A Phase I, Open-Label, Dose-Finding Study of GSK2636771 Administered in Combination with Enzalutamide (Xtandi) in Male Subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC)
IRAS ID
159462
Contact name
Johann de Bono
Contact email
Sponsor organisation
GlaxoSmithKline Research & Development Ltd
Eudract number
2013-005111-27
Research summary
Despite recent advances in the treatment of advanced prostate cancer, relapses are inevitable and metastatic castration-resistant prostate cancer (mCRPC) carries considerable morbidity along with shortened survival. Previous studies have indicated the importance of the phosphoinositide 3 kinase (PI3K) pathway in prostate cancer. A common event in prostate cancer progression is the loss of tumor suppressor phosphatase and tensin homolog (PTEN) in 40-50% of mCRPC patients that results in the activation of the PI3K pathway.
Inhibition of both the androgen receptor (AR) pathway and the PI3K pathway may be more effective than inhibition of either pathway alone in mCRPC. Enzalutamide is an AR inhibitor licensed for the treatment of patients with mCRPC.
This Phase I study will evaluate the safety and tolerability, pharmacokinetics (PK), and clinical activity to determine the recommended Phase 2 Dose (RP2D) and regimen of GSK2636771 in combination with enzalutamide given orally in adult subjects with mCRPC.Approximately 24 eligible subjects will be enrolled in Part 1, the Dose-Escalation Phase to determine the maximum tolerated dose (MTD) of the combination therapy using a modified 3+3 dose escalation procedure. The safety, pharmacokinetics (PK) and clinical efficacy will also be assessed to guide the selection of the RP2D. Once the RP2D has been established, approximately 20 additional subjects will be enrolled in Part 2, the Dose Expansion Phase to further evaluate the safety, PK and preliminary clinical activity. Safety assessments will be performed throughout the study including physical examinations, vital signs, clinical laboratory tests, 12 lead electrocardiograms and monitoring of adverse events. Blood samples will be collected for pharmacokinetic analysis. Subjects will continue treatment until an unacceptable toxicity, disease progression, withdrawal of consent or death occurs. A post-treatment follow-up visit will be performed within 30 days of the last dose of study treatment.
REC name
London - Chelsea Research Ethics Committee
REC reference
14/LO/1598
Date of REC Opinion
7 Oct 2014
REC opinion
Further Information Favourable Opinion