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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00670046
Recruitment Status : Terminated (The study was terminated per the PI decision.)
First Posted : May 1, 2008
Results First Posted : September 28, 2018
Last Update Posted : September 28, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: valproic acid Other: standard of care follow-up Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Controlled Phase II Study of Valproic Acid in Patients With Non-metastatic Biochemical Progression of Prostate Cancer
Study Start Date : May 2008
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Arm I (standard of care)
Patients undergo observation according to the standard of care. Patients complete quality of life questionnaires at baseline, 6 months, and 1 year.
Other: standard of care follow-up
participant follow the standard of care for patient with metastatic prostate cancer

Experimental: 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.
Drug: valproic acid
given orally
Other Name: VPA




Primary Outcome Measures :
  1. Number of Participants Exhibiting an Increase in Observed or Predicted Prostate-specific Antigen (PSA) Doubling Time [ Time Frame: 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 :
  1. Duration of PSA Response as Assessed by PSA Doubling Time (PSADT) [ Time Frame: 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.

  2. Number of Participants Who Achieve a Complete Response [ Time Frame: 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.

  3. Number of Participants Who Achieve a Partial Response [ Time Frame: one year ]
    Partial Response was defined as any participant that showed an increase in PSA doubling time

  4. Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00670046


Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ronald Rodriguez, MD, PhD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00670046    
Other Study ID Numbers: J07122
P30CA068485 ( U.S. NIH Grant/Contract )
CDR0000595004
NA_00010227 ( Other Identifier: JHM IRB )
First Posted: May 1, 2008    Key Record Dates
Results First Posted: September 28, 2018
Last Update Posted: September 28, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
recurrent prostate cancer
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Valproic Acid
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs