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Pharmacokinetic and Efficacy Study of Nordihydroguaiaretic Acid (NDGA) in Non Metastatic Recurrent Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nordihydroguaiaretic Acid (NDGA)
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring NDGA, Prostate Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Rising prostate-specific antigen (PSA) value after local therapy with a PSA doubling time (PSADT) between 6 and 24 months (four or more readings at least two weeks apart within the last six months)

  • Prior definitive therapy for prostate cancer consisting of one of the following:

    1. External beam radiotherapy with or without hormone therapy
    2. Brachytherapy with or without pelvic external beam radiation or hormone therapy
    3. Radical prostatectomy with or without adjuvant or salvage radiation therapy
  • PSA > 1 ng/ml, which has risen serially on two determinations at least one week apart
  • Progressive disease by "Phoenix" consensus definition for patients who have undergone primary radiation therapy (PSA nadir + 2 ng/mL)
  • No metastatic disease

  • Prior adjuvant or neoadjuvant androgen deprivation is permitted, provided:

    1. > 6 months since last day of effective androgen deprivation
    2. Testosterone > 250 ng/dL
    3. Patient is not on intermittent androgen deprivation
  • Karnofsky performance status (KPS) of > 70%
  • Liver Function Tests are within normal range
  • Glycated hemoglobin (HgA1c) < 6%
  • Patients must be four weeks from major surgery or radiotherapy to be eligible

Exclusion Criteria:

  • Presence of another active malignancy other than prostate cancer, or treated squamous/basal cell carcinoma of the skin. Concomitant medical condition which would make it undesirable, in the physician's opinion, for the patient to participate in the protocol or would jeopardize compliance with the protocol requirements
  • Diabetes mellitus, unless diet-controlled
  • Must be off saw palmetto, pomegranate juice, finasteride, or any herbal agent intended to lower PSA for > 4 weeks. Baseline PSADT calculation must occur off of these agents
  • Patients may not have evidence of local-only recurrence of prostate cancer
  • No history of liver disease, including Hepatitis B or C, alcoholic liver disease, or autoimmune liver disease. A prior history of Hepatitis A is allowed provided that baseline liver function tests are within normal limits
  • Patients with castration resistant prostate cancer are ineligible (prostate cancer which has progressed on androgen deprivation therapy with a Luteinizing hormone-releasing hormone (LHRH)-agonist or orchiectomy)

Sites / Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

Prostate Specific Antigen (PSA) Response According to Consensus Criteria
Participants who experienced a PSA decline of at least 50%, confirmed by a second PSA value 4 or more weeks later. The reference PSA for decline was a PSA measured within 2 weeks of beginning study treatment. If at most 1 PSA response was observed among the first 12 patients, then accrual would stop and the trial would close for futility.

Secondary Outcome Measures

Full Information

First Posted
May 12, 2008
Last Updated
March 11, 2014
Sponsor
University of California, San Francisco
Collaborators
Insmed Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT00678015
Brief Title
Pharmacokinetic and Efficacy Study of Nordihydroguaiaretic Acid (NDGA) in Non Metastatic Recurrent Prostate Cancer
Official Title
A Phase II Pharmacokinetic and Efficacy Study of Nordihydroguaiaretic Acid (NDGA) in Non-Metastatic Recurrent Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Terminated
Why Stopped
Per protocol - interim analysis showed no significant PSA declines among the first 12 patients after 3 cycles of treatment
Study Start Date
May 2008 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Insmed Incorporated

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase II, single center study measuring the pharmacokinetic parameters of NDGA administration and assessing the proportion of patients who experience a 50% decline in PSA.
Detailed Description
This study is a phase II trial of NDGA in patients with hormone-sensitive non-metastatic prostate cancer with a pharmacokinetics component. The first six patients enrolled will be treated with a single 750 mg dose of oral NDGA on day -7 with measurement of pharmacokinetic parameters over eight hours after the dose, then begin treatment with 2000 mg of oral NDGA daily. Every four weeks, measurement of pharmacokinetic parameters at steady state will be done for all patients. All patients will continue dosing with NDGA and will be followed for PSA response and for safety. Measurement of pharmacokinetics for a 750 mg dose has been chosen to evaluate levels with the dosage that patients will be taking at one time point during the day (this is roughly one-third of the daily dose, which is administered in three divided doses).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
NDGA, Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nordihydroguaiaretic Acid (NDGA)
Intervention Description
NDGA 2000mg daily
Primary Outcome Measure Information:
Title
Prostate Specific Antigen (PSA) Response According to Consensus Criteria
Description
Participants who experienced a PSA decline of at least 50%, confirmed by a second PSA value 4 or more weeks later. The reference PSA for decline was a PSA measured within 2 weeks of beginning study treatment. If at most 1 PSA response was observed among the first 12 patients, then accrual would stop and the trial would close for futility.
Time Frame
Monthly, up to 29 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Rising prostate-specific antigen (PSA) value after local therapy with a PSA doubling time (PSADT) between 6 and 24 months (four or more readings at least two weeks apart within the last six months) Prior definitive therapy for prostate cancer consisting of one of the following: External beam radiotherapy with or without hormone therapy Brachytherapy with or without pelvic external beam radiation or hormone therapy Radical prostatectomy with or without adjuvant or salvage radiation therapy PSA > 1 ng/ml, which has risen serially on two determinations at least one week apart Progressive disease by "Phoenix" consensus definition for patients who have undergone primary radiation therapy (PSA nadir + 2 ng/mL) No metastatic disease Prior adjuvant or neoadjuvant androgen deprivation is permitted, provided: > 6 months since last day of effective androgen deprivation Testosterone > 250 ng/dL Patient is not on intermittent androgen deprivation Karnofsky performance status (KPS) of > 70% Liver Function Tests are within normal range Glycated hemoglobin (HgA1c) < 6% Patients must be four weeks from major surgery or radiotherapy to be eligible Exclusion Criteria: Presence of another active malignancy other than prostate cancer, or treated squamous/basal cell carcinoma of the skin. Concomitant medical condition which would make it undesirable, in the physician's opinion, for the patient to participate in the protocol or would jeopardize compliance with the protocol requirements Diabetes mellitus, unless diet-controlled Must be off saw palmetto, pomegranate juice, finasteride, or any herbal agent intended to lower PSA for > 4 weeks. Baseline PSADT calculation must occur off of these agents Patients may not have evidence of local-only recurrence of prostate cancer No history of liver disease, including Hepatitis B or C, alcoholic liver disease, or autoimmune liver disease. A prior history of Hepatitis A is allowed provided that baseline liver function tests are within normal limits Patients with castration resistant prostate cancer are ineligible (prostate cancer which has progressed on androgen deprivation therapy with a Luteinizing hormone-releasing hormone (LHRH)-agonist or orchiectomy)
Facility Information:
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21971890
Citation
Friedlander TW, Weinberg VK, Huang Y, Mi JT, Formaker CG, Small EJ, Harzstark AL, Lin AM, Fong L, Ryan CJ. A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer. Oncol Rep. 2012 Jan;27(1):3-9. doi: 10.3892/or.2011.1487. Epub 2011 Oct 4.
Results Reference
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Pharmacokinetic and Efficacy Study of Nordihydroguaiaretic Acid (NDGA) in Non Metastatic Recurrent Prostate Cancer

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