Valproic Acid in Treating Patients With Progressive, Non-Metastatic Prostate Cancer - Full Text View

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00670046

Purpose

RATIONALE: Valproic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether valproic acid is more effective than observation in treating patients with prostate cancer.

PURPOSE: This randomized phase II trial is studying how well valproic acid works in treating patients with progressive, non-metastatic prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Drug: valproic acid Procedure: observation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Randomized, Controlled Phase II Study of Valproic Acid in Patients With Non-Metastatic Biochemical Progression of Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Divalproex sodium Valproic acid Valproate Sodium

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Percentage of patients exhibiting observed or predicted prostate-specific antigen (PSA) doubling time > 10 months after initiation of the study [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of PSA response [ Designated as safety issue: No ]
Percentage of patients who achieve a complete response [ Designated as safety issue: No ]
Percentage of patients who achieve a partial response [ Designated as safety issue: No ]
Self-perceived functionality, psychosocial well-being, and quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	May 2008
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (observation): No Intervention Patients undergo observation according to standard of care. Patients complete quality of life questionnaires at baseline, 6 months, and 1 year.	Procedure: observation no intervention
Arm II (valproic acid): Experimental Patients receive oral valproic acid twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, 6 months, and 1 year.	Drug: valproic acid given orally

Detailed Description:

OBJECTIVES:

Primary

Assess whether treatment with valproic acid (a type I histone deacetylase inhibitor) can alter the kinetics of prostate-specific antigen (PSA) progression in patients with non-metastatic prostate cancer and biochemical progression.

Secondary

Determine the duration of PSA response.
Assess the percentage of patients who achieve a complete response.
Assess the percentage of patients who achieve a partial response.
Assess the quality of life of these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 arms.

Arm I (observation): Patients undergo observation according to standard of care.
Arm II (valproic acid): Patients receive oral valproic acid twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, 6 months, and 1 year.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed prostate cancer
- Asymptomatic, non-metastatic disease
Biochemical progression after definitive local therapy (radical prostatectomy)
- Most recent prostate-specific antigen (PSA) level ≥ 1.0 ng/mL AND rising over the prior value
- No clinical or radiological evidence of local progression
PSA doubling time (DT) < 10 months after local therapy (in patients who have not received prior hormone therapy)
- At least three PSA values (each at least 4 weeks apart) are required to calculate the PSA-DT
No clinical or radiological evidence of metastatic disease, including bone metastasis

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 3 months
Total bilirubin normal
AST/ALT < 2.5 times upper limit of normal
Creatinine ≤ 2.5 mg/dL
Platelet count > 125,000/mm^3
PT and aPTT ≤ 1.3 times above the standard reference
Albumin ≥ 3.5 g/dL
Geographically accessible and willing to participate in all stages of study treatment
No active second malignancy
No known HIV positivity
No active, uncontrolled infection (e.g., hepatitis A, B, or C infection)
No history of allergic reactions attributed to compounds of similar chemical or biological composition to valproic acid
No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal study treatment and follow-up
No history of hepatic disease or significant hepatic dysfunction
No history of pancreatitis
No history of seizure disorder or clinically treated bipolar disorder

PRIOR CONCURRENT THERAPY:

More than 6 months since prior hormone therapy
No prior valproic acid
At least 2 weeks since prior drugs specifically known to interact with valproic acid including, but are not limited to, aspirin, felbamate, rifampin, amitriptyline/nortriptyline, carbamazepine, clonazepam, diazepam, ethosuximide, lamotrigine, phenobarbital, primidone, phenytoin, tolbutamide, warfarin, or zidovudine
No concurrent systemic chemotherapy for prostate cancer
No other concurrent investigational drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670046

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 jhcccro@jhmi.edu

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Ronald Rodriguez, MD, PhD

Sidney Kimmel Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Ronald Rodriguez )
Study ID Numbers:	CDR0000595004, JHOC-J07122, JHOC-NA_00010227
Study First Received:	April 30, 2008
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00670046 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent prostate cancer
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer

Study placed in the following topic categories:

Neurotransmitter Agents
Tranquilizing Agents
Genital Neoplasms, Male
Prostatic Diseases
Disease Progression
Psychotropic Drugs
Central Nervous System Depressants

Urogenital Neoplasms
Genital Diseases, Male
Antimanic Agents
Valproic Acid
Recurrence
Prostatic Neoplasms
Anticonvulsants

Additional relevant MeSH terms:

Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Genital Neoplasms, Male
Prostatic Diseases
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors
Urogenital Neoplasms
Genital Diseases, Male

Antimanic Agents
Valproic Acid
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
GABA Agents
Central Nervous System Agents
Prostatic Neoplasms
Anticonvulsants

ClinicalTrials.gov processed this record on September 03, 2009