Clinical trial NCT00670046: Valproic Acid in Treating Patients With Progressive, Non-Metastatic Prostate Cancer
Official title: Randomized, Controlled Phase II Study of Valproic Acid in Patients With Non-metastatic Biochemical Progression of Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: recurrent prostate cancer
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-05-01
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Participants Exhibiting an Increase in Observed or Predicted Prostate-specific Antigen (PSA) Doubling Time
timeFrame: 1 year
Secondary outcomes:
measure: Duration of PSA Response as Assessed by PSA Doubling Time (PSADT)
timeFrame: pre-study, mid-study, end of study (up to 1 year)
measure: Number of Participants Who Achieve a Complete Response
timeFrame: one year
measure: Number of Participants Who Achieve a Partial Response
timeFrame: one year
measure: Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score
timeFrame: at time of enrollment, mid-study, end of study (up to 1 year)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Ronald Rodriguez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: