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

Phase 2

Terminated

Conditions: Prostate Cancer

Interventions: Other: standard of care follow-up
Drug: valproic acid

Registration Number: NCT00670046

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (standard of care)	standard of care follow-up	Patients undergo observation according to the standard of care. Patients complete quality of life questionnaires at baseline, 6 months, and 1 year.
Arm II (valproic acid)	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Exhibiting an Increase in Observed or Predicted Prostate-specific Antigen (PSA) Doubling Time	1 year	Number of participants exhibiting an increase in observed or predicted prostate-specific antigen (PSA) doubling time after initiation of the study. Blood was drawn monthly during study period (1 year), serum PSA was measured \& PSADT calculated. A doubling time of \> 10 month is defined as complete response (3. Secondary Outcome) and this criteria was based on the Pound et al JAMA 1999, Vol 281(No 17) pgs 1591-1697 paper. Any increase in PSADT is defined as partial response (4. Secondary Outcome).

Secondary Outcome Measures

Name	Time	Method
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score	at time of enrollment, mid-study, end of study (up to 1 year)	Study questionnaire, known as "Functional Assessment of Cancer Therapy - Prostate (FACT-P), were given to participant to complete during study participation. FACT-P is a validated tool to assess self-perceived functionality, psychosocial well-being, and quality of life; and the scoring of the questionnaire was based on the technique published by FACIT (Functional Assessment of Chronic Illness Therapy). The FACT-P is a 39-item questionnaire, with each item being scored from on a Likert scale of 0-4. The total score ranges from 0-156, with a higher score reflecting a better outcome.
Number of Participants Who Achieve a Complete Response	one year	Complete response was defined as PSA Doubling Time increasing to greater than 10 months. Blood was drawn monthly during study period (1 year), serum PSA was measured \& PSADT calculated. The \> 10 month criteria was based on the Pound et al JAMA 1999, Vol 281(No 17) pgs 1591-1697 paper.
Duration of PSA Response as Assessed by PSA Doubling Time (PSADT)	pre-study, mid-study, end of study (up to 1 year)	Serum PSA was measured once a month, each month for the one year the subjects were on the protocol. PSA Doubling time is defined as the duration for PSA levels in the blood to increase by 100 percent, and is calculated based on the rate of change in serum PSA values. Prostate-specific antigen doubling time (PSADT) was calculated by natural log of 2 (0.693) divided by the slope of the relationship between the log of PSA and time of PSA measurement for each patient (Pound et al JAMA 1999, Vol 281(No 17) pgs 1591-1697), therefore it can be much greater than the 12 months that we followed the patients for. PSADT was calculated for pre enrollment, at the mid point of the study \& at the end of study.
Number of Participants Who Achieve a Partial Response	one year	Partial Response was defined as any participant that showed an increase in PSA doubling time