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

Primary Purpose

Prostate Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
valproic acid
standard of care follow-up
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring recurrent prostate cancer, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, stage IV prostate cancer

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Arm I (standard of care)

Arm II (valproic acid)

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
Number of Participants Who Achieve a Partial Response
Partial Response was defined as any participant that showed an increase in PSA doubling time
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.

Full Information

First Posted
April 30, 2008
Last Updated
September 26, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00670046
Brief Title
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

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated per the PI decision.
Study Start Date
May 2008 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (standard of care)
Arm Type
Other
Arm Description
Patients undergo observation according to the standard of care. Patients complete quality of life questionnaires at baseline, 6 months, and 1 year.
Arm Title
Arm II (valproic acid)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
valproic acid
Other Intervention Name(s)
VPA
Intervention Description
given orally
Intervention Type
Other
Intervention Name(s)
standard of care follow-up
Intervention Description
participant follow the standard of care for patient with metastatic prostate cancer
Primary Outcome Measure Information:
Title
Number of Participants Exhibiting an Increase in Observed or Predicted Prostate-specific Antigen (PSA) Doubling Time
Description
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).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Duration of PSA Response as Assessed by PSA Doubling Time (PSADT)
Description
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.
Time Frame
pre-study, mid-study, end of study (up to 1 year)
Title
Number of Participants Who Achieve a Complete Response
Description
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.
Time Frame
one year
Title
Number of Participants Who Achieve a Partial Response
Description
Partial Response was defined as any participant that showed an increase in PSA doubling time
Time Frame
one year
Title
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score
Description
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.
Time Frame
at time of enrollment, mid-study, end of study (up to 1 year)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald Rodriguez, MD, PhD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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