Neoadjuvant Androgen Depletion in Combination With Vorinostat Followed by Radical Prostatectomy for Localized Prostate Cancer: Total Androgen-Receptor Gene Expression Targeted Therapy (TARGET)
I. Determine the rate of pathologic complete response in patients with localized prostate
cancer treated with androgen depletion therapy (ADT) and vorinostat (SAHA) before radical
I. Determine and evaluate pre- and post-treatment levels of PSA, testosterone, DHT, DHEA,
and DHEA-S in blood.
II. Determine and evaluate pre- and post-treatment levels of testosterone, androstenedione,
androstenediol, DHT, DHEA, and DHEA-S in prostate tissue.
III. Determine and evaluate gene and protein expression analysis including AR target genes,
PSA and TMPRSS2 (transmembrane protease, serine 2), in pre-treatment biopsy and
post-treatment radical prostatectomy specimens.
IV. Perform exploratory gene microarray analysis. V. Determine and evaluate the safety and
tolerability of ADT in combination with vorinostat as assessed by physical examinations,
adverse events, and laboratory assessments.
OUTLINE: This is a multicenter study. Patients receive bicalutamide orally (PO) once daily
for 1 month and leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC)
once a month until surgery. Patients also receive vorinostat (SAHA) PO once daily beginning
on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the
day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy.
Patients with positive surgical margins undergo immediate adjuvant external beam
radiotherapy to the prostatic fossa, based on the judgment of the treating physician.
Patients undergo tissue sample collection at baseline and during surgery for laboratory
correlative studies. Biomarker expression analysis is performed on the samples by
quantitative real time reverse transcription-polymerase chain reaction (RT-PCR) and
immunohistochemistry (IHC) for HDAC-regulated target genes, AR and AR-regulated genes, PSA
and TMPRSS2. If adequate material is available, fresh frozen tissue is analyzed by
microarray analysis for predictors of response and resistance to therapy. Hormonal levels
are also measured in these tissue samples. Patients also undergo blood sample collection
periodically to measure hormone and PSA levels.
After completion of study therapy, patients are followed every 3 months for up to 1 year.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic complete response at the time of surgery
A Simon 2-stage optimal design that differentiates between response probabilities of 0.05 and 0.20 will be used in the analysis of the pathological complete response at the time of surgery (Type I error 10% and power 90%).
At 12 weeks
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|