Androgen Deprivation Therapy and Vorinostat Followed by Radical Prostatectomy in Treating Patients With Localized Prostate Cancer (TARGET)

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Prostate Adenocarcinoma; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage III Prostate Cancer; Stage IIB Prostate Cancer

Treatments: Procedure: Therapeutic Conventional Surgery; Drug: Leuprolide Acetate; Drug: Bicalutamide; Other: Laboratory Biomarker Analysis; Drug: Goserelin Acetate; Drug: Vorinostat

Study type: Interventional

Funder types: NIH

Identifiers

NCT00589472

N01CM62206 (U.S. NIH Grant/Contract)

NCI-2009-00238 (Registry Identifier)

7864 (Other Identifier)

P30CA008748 (U.S. NIH Grant/Contract)

06-160

CDR0000579559

MSKCC-06160

MSKCC IRB 06-160

N01CM62205 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This phase II trial studies how well androgen deprivation therapy and vorinostat followed by radical prostatectomy works in treating patients with prostate cancer that has not spread to other parts of the body. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin acetate, and leuprolide acetate, may lessen the amount of androgens made by the body. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving androgen deprivation therapy and vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Full description

PRIMARY OBJECTIVES:

I. To determine the rate of pathologic complete response in patients with localized prostate cancer treated with androgen depletion therapy (ADT) and oral vorinostat administered for a minimum of 6 weeks and maximum of 8 weeks before radical prostatectomy.

SECONDARY OBJECTIVES:

I. To determine and evaluate pre- and post-treatment levels of prostate-specific antigen (PSA), testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-dulfate (DHEA-S) in blood.

II. To determine and evaluate pre- and post-treatment levels of testosterone, androstenedione, androstenediol, DHT, DHEA, and DHEA-S in prostate.

III. To determine and evaluate gene and protein expression analysis including androgen receptor (AR) target genes, PSA and TMPRSS2 (transmembrane protease, serine 2), in pre-treatment biopsy and post-treatment radical prostatectomy.

IV. To determine and evaluate exploratory gene microarray analysis. V. To determine and evaluate the safety and tolerability of ADT in combination with vorinostat (SAHA) as assessed by physical examinations, adverse events, and laboratory assessments.

OUTLINE:

Patients receive bicalutamide orally (PO) once daily (QD) for 1 month and leuprolide acetate intramuscularly (IM) or goserelin acetate subcutaneously (SC) once a month until surgery. Patients also receive vorinostat PO QD 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.

After completion of study treatment, patients are followed every 3 months for up to 1 year.

Enrollment: 19 patients

Sex: Male

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologic documentation of prostatic adenocarcinoma in 3 or more biopsy cores, of which at least 1 core demonstrates > 30% involvement with tumor; confirmation of localized disease by magnetic resonance imaging (MRI) with endorectal probe if available

• No evidence of distant disease on a:

  • Computed tomography (CT) or MRI of the abdomen and pelvis
  • Radionuclide bone scan (with plain film or MRI confirmation as clinically indicated)

• Appropriate candidate for radical prostatectomy

  • Adequate cardiac function (evidence of cardiac disease should be evaluated to determine appropriateness of patient as a surgical candidate)
  • Candidates may have a history of deep vein thrombosis, pulmonary embolism, and/or cerebrovascular accident, or require concomitant systemic anticoagulation, if otherwise deemed to be suitable for radical prostatectomy

• White blood cell (WBC) > 3000/uL

• Platelets > 150,000/uL

• Creatinine < 2 mg/dL

• Serum PSA < 100 ng/mL

• Bilirubin < 1.5 X ULN (institutional upper limits of normal)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2 X ULN

• Karnofsky performance status > 70%

• Willingness to undergo pretreatment transrectal ultrasound-guided prostate needle biopsy (optional)

• Willingness to use adequate contraceptive methods during study therapy and for at least 3 months after completion of therapy

• Ability to understand and willingness to sign a written informed consent document

Exclusion criteria

• Evidence of small-cell, transitional-cell, or neuroendocrine pathologic features

• Prior hormonal therapy with (e.g. 5-alpha-reductase inhibitors, gonadotropin hormone releasing analogs, steroids, megestrol acetate, or nonstudy-related antiandrogens), chemotherapy, or herbal medications administered with the intent to treat the patient's malignancy

  • Patients on valproic acid (a histone-deacetylase inhibitor) to treat prostate cancer are not eligible

• History of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would compromise compliance with study requirements

• Currently active secondary malignancy (as determined by the treating physician) other than non-melanoma skin cancer

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Experimental group

Description:

Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD 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.

Treatment:

Drug: Vorinostat

Drug: Goserelin Acetate

Other: Laboratory Biomarker Analysis

Drug: Bicalutamide

Drug: Leuprolide Acetate

Procedure: Therapeutic Conventional Surgery