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

Prostate Cancer Clinical Trial

Official title:

Randomized, Controlled Phase II Study of Valproic Acid in Patients With Non-metastatic Biochemical Progression of Prostate Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00670046
• Other study ID #: J07122
• Secondary ID: P30CA068485CDR00
• Status: Terminated
• Phase: Phase 2
• Start date: May 2008
• Est. completion date: July 2012

Study information

• Verified date: September 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• valproic acid
given orally

Other:
• standard of care follow-up
participant follow the standard of care for patient with metastatic prostate cancer

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Exhibiting an Increase in Observed or Predicted Prostate-specific Antigen (PSA) Doubling Time	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).	1 year
Secondary	Duration of PSA Response as Assessed by PSA Doubling Time (PSADT)	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.	pre-study, mid-study, end of study (up to 1 year)
Secondary	Number of Participants Who Achieve a Complete Response	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.	one year
Secondary	Number of Participants Who Achieve a Partial Response	Partial Response was defined as any participant that showed an increase in PSA doubling time	one year
Secondary	Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score	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.	at time of enrollment, mid-study, end of study (up to 1 year)