Neoadjuvant Androgen Depletion in Combination With Vorinostat Followed by Radical Prostatectomy for Localized Prostate Cancer: Total Androgen-Receptor Gene Expression Targeted Therapy (TARGET)
18 Years
N/A
Male
Adenocarcinoma of the Prostate, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer
Trial Information
Neoadjuvant Androgen Depletion in Combination With Vorinostat Followed by Radical Prostatectomy for Localized Prostate Cancer: Total Androgen-Receptor Gene Expression Targeted Therapy (TARGET)
PRIMARY OBJECTIVES:
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
prostatectomy.
SECONDARY OBJECTIVES:
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.
Inclusion Criteria:
- Histologically confirmed adenocarcinoma of the prostate
- At least 3 biopsy cores positive for cancer, of which at least 1 core
demonstrates > 30% involvement with tumor
- Confirmation of localized disease by MRI with endorectal probe, if available
- Serum PSA < 100 ng/mL
- Candidate for radical prostatectomy
- No evidence of small cell, transitional cell, or neuroendocrine pathologic features
- No evidence of distant disease on CT scan or MRI of the abdomen and pelvis and on
radionuclide bone scan (with plain film or MRI confirmation as clinically indicated)
- Karnofsky performance status 80-100%
- WBC > 3,000/µL
- Platelet count > 150,000/µL
- Creatinine < 2 mg/dL
- Bilirubin < 1.5 times upper limit of normal (ULN)
- AST/ALT < 2 times ULN
- Adequate cardiac function (evidence of cardiac disease should be evaluated to
determine appropriateness of patient as a surgical candidate)
- May have a history of deep vein thrombosis, pulmonary embolism, and/or
cerebrovascular accident, if otherwise deemed to be suitable for radical
prostatectomy
- Must use adequate contraceptive methods during and for at least 3 months after
completion of study therapy
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to vorinostat (SAHA)
- No concurrent uncontrolled illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia
- No psychiatric illness/social situation that would compromise compliance with study
requirements
- No currently active secondary malignancy (as determined by the treating physician)
other than nonmelanoma skin cancer
- No prior hormonal therapy (e.g., 5-alpha-reductase inhibitors, gonadotropin hormone
releasing analogs, steroids, megestrol acetate, or nonstudy-related antiandrogens)
with the intent to treat the malignancy
- No prior chemotherapy or herbal medications administered with the intent to treat the
malignancy
- At least 2 weeks since prior valproic acid
- No concurrent valproic acid to treat prostate cancer
- No other concurrent antineoplastic therapy
- Concurrent systemic anticoagulation allowed
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathologic complete response at the time of surgery
Outcome Description:
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%).
Outcome Time Frame:
At 12 weeks
Safety Issue:
No
Principal Investigator
Susan Slovin
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00238
NCT ID:
NCT00589472
Start Date:
November 2007
Completion Date:
Related Keywords:
- Adenocarcinoma of the Prostate
- Stage I Prostate Cancer
- Stage IIA Prostate Cancer
- Stage IIB Prostate Cancer
- Stage III Prostate Cancer
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Prostatic Neoplasms
Name | Location |
|---|---|
| Memorial Sloan Kettering Cancer Center | New York, New York 10021 |
