RATIONALE: Temsirolimus and vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving temsirolimus together with vorinostat may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of temsirolimus and vorinostat in treating patients with metastatic prostate cancer.
PRIMARY OBJECTIVES: I. To determine the safety, tolerability and recommended Phase II dose of temsirolimus in combination with vorinostat in patients with metastatic, hormone refractory, chemoresistant prostate cancer. II. To obtain preliminary evidence of response in prostate cancer patients treated with temsirolimus and vorinostat. SECONDARY OBJECTIVES: I. To determine the partial and complete objective response rates in metastatic hormone-refractory, chemo-resistant prostate cancer patients with measurable disease treated with temsirolimus and vorinostat. II. To determine the progression free survival and overall survival in patients with metastatic hormone refractory, chemo-resistant prostate cancer. III. To determine the PSA response, the duration of PSA response, time to PSA progression, PSA doubling time and PSA slope in metastatic hormone refractory, chemo-resistant prostate cancer patients treated with temsirolimus and vorinostat. IV. To assess changes in expression levels of bone remodeling markers (N telopeptides and bone alkaline phosphatase) and angiogenesis-related gene and protein expression (VEGF/HIF1-alpha) in blood and circulating tumor cells, and when available, in tissue, and correlate them with cancer and treatment related outcomes. V. To assess the changes in tumor metabolism with FDG/IIC-Choline PET/CT scan. OUTLINE: Patients receive oral vorinostat once daily on days 1-14 and temsirolimus IV on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days and then every 3 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
The Sydney Kimmel Comprehensive Center at John Hopkins
Baltimore, Maryland, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Frequencies of DLT and toxicity
Time frame: 4 yrs
Adverse events
Time frame: 4 years
Median survival, median progression-free survival, and frequency of deaths
Time frame: 4 years
PSA response
Time frame: Every 2 cycles of treatment
Changes in expression of bone remodeling markers and angiogenesis-related gene and protein expression
Time frame: Prior to each cycle
Changes in tumor metabolism as assessed by PET/CT scan
Time frame: Prior to each cycle
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