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

Johns Hopkins Medicine

Status and phase: Terminated; Phase 2

Conditions: Prostate Cancer

Treatments: Other: standard of care follow-up; Drug: valproic acid

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00670046

P30CA068485 (U.S. NIH Grant/Contract)

NA_00010227 (Other Identifier)

J07122

CDR0000595004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: Male

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 2 patient groups

Arm I (standard of care)

Other group

Description:

Patients undergo observation according to the standard of care. Patients complete quality of life questionnaires at baseline, 6 months, and 1 year.

Treatment:

Other: standard of care follow-up

Arm II (valproic acid)

Experimental group

Description:

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.

Treatment:

Drug: valproic acid