ARN 509 Plus Everolimus in Men With Progressive Metastatic Castration-Resistant Prostate Cancer After Treatment With Abiraterone Acetate
|ClinicalTrials.gov Identifier: NCT02106507|
Recruitment Status : Active, not recruiting
First Posted : April 8, 2014
Last Update Posted : May 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: apalutamide Drug: Everolimus||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1b Study of ARN 509 Plus Everolimus in Men With Progressive Metastatic Castration-Resistant Prostate Cancer After Treatment With Abiraterone Acetate|
|Actual Study Start Date :||April 2014|
|Estimated Primary Completion Date :||April 2018|
|Estimated Study Completion Date :||April 2018|
Experimental: Progressive Metastatic Castration-Resistant Prostate Cancer
This is a single-institution Phase 1b dose-escalation study in which eligible patients with progressive mCRPC will receive oral doses of apalutamide in combination with everolimus.
apalutamide, 240 mg/day, oralDrug: Everolimus
5 mg/day of everolimus dose of everolimus will be escalated to 10 mg/day depending on the safety seen during dose escalation and steady-state trough drug levels as recommended
- safety [ Time Frame: 2 years ]Safety will be evaluated according to the NCI Common Terminology Criteria for Adverse Events V4.0 (CTCAE). Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests throughout the conduct of the study.
- pharmacokinetics [ Time Frame: 2 years ]Pharmacokinetic parameters (Cmax, Tmax, AUC(INF), AUC(TAU), will be derived from blood to obtain everolimus concentration or plasma to obtain apalutamide and it's major metabolite concentration versus time data for patients in the dose escalation cohorts.
- maximum tolerated dose (MTD) [ Time Frame: 2 years ]The first phase of the study will examine the safety of apalutamide in combination with everolimus in patients with metastatic castration-resistant prostate cancer. Up to 2 dose levels will be tested. A standard "3 plus 3" dose escalation rule will be used in order to determine the MTD/RP2D. Patients will be treated in cohorts of three and the dosage will be escalated if the clinical toxicity is acceptable. The MTD is defined as the highest dose with an observed incidence of dose limiting toxicity (DLT) in no more than one out of six patients treated at a particular dose level.
- anti-tumor activity [ Time Frame: 2 years ]Tumor biopsies pre- and post-treatment will be collected to evaluate for downstream indicators of PI3K pathway modulation, including pS6K, p4EBP1, pAKT, AR, PHLLP 1 and 2, and additional pathways of interest if safe and feasible per treating investigator. In lieu of biopsy, if a patient is having an elective or clinical resection/surgery and tissue is already being removed, some of that tissue may be collected for research purposes to fulfill the biopsy requirement for that timepoint. These biomarkers will be measured at baseline and cycle 2 and after treatment to explore the association between changes in the tumor biomarkers and progression-free survival.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02106507
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Dana Rathkopf, MD||Memorial Sloan Kettering Cancer Center|