Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI, Other	CDR0000478886 CCUM-HUM00002854, UMCC-2005.127, NCI-6862, NCT00330161

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well vorinostat works in treating patients with progressive metastatic prostate cancer.

Further Study Information

OBJECTIVES:

Primary

• Evaluate the efficacy of vorinostat (SAHA), as measured by the proportion of patients who do not progress at 6 months, in patients with castrate metastatic prostate cancer that has progressed on 1 prior chemotherapy regimen.

Secondary

• Evaluate the safety of SAHA in these patients.

• Assess the objective response rate in patients with measurable disease treated with SAHA.

• Assess the rate of prostate-specific antigen (PSA) decline of ≥ 50% in these patients.

• Assess progression-free and median survival of these patients.

• Evaluate pre- and post-treatment tumor biopsies for the presence of changes in the expression of androgen receptor (AR) and heat shock protein-90 (Hsp90) client proteins, thioredoxin, thioredoxin binding protein, histone deacetylase (HDAC) 3 (class I), HDAC 7 (class II), enhancer of zestes homolog 2 (EZH2), and p21 expression.

• Determine the effects of SAHA on interleukin-6 (IL-6), soluble IL-6 receptor, and soluble gp130 levels in the blood.

OUTLINE: This is a multicenter study.

Patients receive oral vorinostat (SAHA) once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 4 courses receive an additional 3 courses. All other patients may continue treatment in the absence of disease progression or unacceptable toxicity.

Blood samples are taken on day 15 of course 1, day 1 of course 2, during the last week of course 4, and at completion of study treatment. Blood is examined for interleukin (IL)-6, IL-6 receptor, and gp130 levels.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed prostate cancer

• Metastatic disease

• Measurable and/or bony disease that has progressed despite androgen-deprivation therapy and 1 prior chemotherapy regimen for castrate metastatic disease

• Prostate specific antigen (PSA) progression

• Must have a minimum PSA ≥ 5 ng/mL

• At least 2 rises in PSA documented over a reference value (measure 1)

• First rising PSA (measure 2) must be taken at least 7 days after the reference value

• Second rising PSA (measure 3) must be taken at least 7 days after measure 2 and be greater than the second measure OR a fourth PSA (measure 4) taken is greater than the second measure

• Testosterone < 50 ng/dL

• Must continue primary androgen deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if no prior orchiectomy

• No known brain metastases

• Treated controlled epidural disease allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy > 6 months

• WBC ≥ 3,000/mm³

• Absolute neutrophil count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Creatinine < 2 mg/dL

• Bilirubin normal

• AST/ALT ≤ 2.5 times upper limit of normal

• Fertile patients must use effective contraception

• No New York Heart Association class III or IV heart disease

• No active angina pectoris

• No myocardial infarction within the last 6 months

• No symptomatic congestive heart failure

• No cardiac arrhythmia

• No other significant cardiovascular disease

• Patients who require additional diagnostic testing due to either history or clinical findings must meet the following additional criteria:

• Ejection fraction > 45% by radionuclide angiocardiography (RNCA)

• No evidence of ventricular aneurysm or other abnormal wall motion by RNCA

• No reversible defect by stress thallium test

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA)

• No psychiatric illness/social situation that would limit compliance with study requirements

• No ongoing or active infection

• No other "currently active" malignancy other than nonmelanoma skin cancer

• Patients are not considered to have a "currently active" malignancy if they have completed therapy and have no evidence of disease

• No other uncontrolled intercurrent illness

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 4 weeks since prior major surgery

• At least 4 weeks since prior radiotherapy

• At least 2 weeks since prior valproic acid

• No prior radiopharmaceuticals

• No other concurrent anticancer investigational or commercial agents or therapies, including hormonal agents such as steroids, megestrol, or antiandrogens, or herbal medications

• LHRH analogue allowed

• Low-dose megestrol to treat hot flashes allowed

• No concurrent oral anti-androgens

• A washout period of 4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide is required if a patient has continued on antiandrogen therapy as part of combined androgen deprivation and has never had antiandrogen withdrawal despite progression on combined androgen deprivation

• No concurrent combination antiretroviral therapy for HIV-positive patients

Trial Contact Information

Trial Lead Organizations/Sponsors

University of Michigan Comprehensive Cancer Center

Maha Hadi A. Hussain

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00330161
Information obtained from ClinicalTrials.gov on October 06, 2009

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