Enzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer
The purpose of this study is to determine the safety and efficacy of a novel combination of agents, enzalutamide and everolimus, for the treatment of patients with metastatic castrate-resistant prostate cancer who have never received prior chemotherapy, or who have previously received docetaxel chemotherapy and have progressive disease.
Prostate Cancer, Castrate-resistant
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Enzalutamide Plus Everolimus in Men With Metastatic Castrate-Resistant Prostate Cancer: A Phase I Study With a Maximum Tolerated Dose Expansion Cohort|
- Escalating doses of everolimus will be tested with standard dose enzalutamide. [ Time Frame: 6-8 months ] [ Designated as safety issue: Yes ]Establish the optimal daily dose of everolimus to be administered in conjunction with a standard daily dose of enzalutamide
- Prostate-specific antigen (PSA) response rate decline of greater than 50 percent. [ Time Frame: 36 months ] [ Designated as safety issue: No ]Obtain preliminary information regarding the efficacy of the combination in the treatment of men with docetaxel-refractory metastatic prostate cancer
- Number of patients with serious and non-serious adverse events. [ Time Frame: every 4 weeks up to 24 months ] [ Designated as safety issue: Yes ]Evaluate the safety of the combination per CTCAE v4.0, every 4 weeks from date of first study treatment until the date of documented progression, up to 24 months.
- Levels of everolimus in blood samples collected from patients at selected timepoints prior to everolimus dosing during the first 3 cycles of treatment. [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]
- PSA response rate (decline of greater than 85 %) [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]
- Time to PSA progression [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]Restaging will occur every 8 weeks from date of first treatment until date of first PSA progression.
- Overall Response Rate (ORR) [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]Soft tissue response rate [percentage of complete responders (CR) and partial responders (PR) per RECIST v1.1]
- Progression-free survival (PFS) [ Time Frame: every 8 weeks up to 24 months ] [ Designated as safety issue: No ]Restaging will occur every 8 weeks from date of first treatment until date of first progression, or date of death from any cause, whichever comes first - up to 24 months.
|Study Start Date:||August 2014|
|Estimated Study Completion Date:||May 2017|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
Experimental: Everolimus and Enzalutamide
Dose Escalation Phase (18 patients): 3-6 patients will be treated at each dose level until the Maximum Tolerated Dose (MTD) is determined.
Dose Expansion Phase (23 patients): Everolimus and Enzalutamide to be administered using the MTD determined in the dose escalation phase.
Other Names:Drug: Enzalutamide
Other Name: MDV3100
This is a multi-center, open-label, Phase I study with an expansion cohort, in patients with metastatic Castrate-Resistant Prostate Cancer (CRPC) who are chemotherapy-naive or have previously received docetaxel chemotherapy and have progressive disease at the time of study entry. The dose escalation phase of this study will establish the optimum daily dose of everolimus that can be delivered along with a standard daily dose of enzalutamide to patients with metastatic CRPC. Eligible patients must have evaluable (elevated PSA) or measurable disease (per RECIST v1.1). Following completion of the dose escalation phase, an additional cohort of patients will be treated at the maximum tolerated dose (MTD) to give preliminary information regarding the efficacy of this combination.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02125084
|Contact: Sarah Cannon Research Institute||1-877-691-7274||askSarah@scresearch.net|
|United States, Ohio|
|Oncology Hematology Care Inc.||Recruiting|
|Cincinnati, Ohio, United States, 45242|
|United States, Tennessee|
|Tennessee Oncology PLLC||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Study Chair:||John D. Hainsworth, MD||SCRI Development Innovations, LLC|