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

This study has been terminated.
(Per protocol - interim analysis showed no significant PSA declines among the first 12 patients after 3 cycles of treatment)
Sponsor:
Collaborator:
Insmed
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00678015
First received: May 12, 2008
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Nordihydroguaiaretic Acid (NDGA)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Pharmacokinetic and Efficacy Study of Nordihydroguaiaretic Acid (NDGA) in Non-Metastatic Recurrent Prostate Cancer

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Prostate Specific Antigen (PSA) Response According to Consensus Criteria [ Time Frame: Monthly, up to 29 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 12
Study Start Date: May 2008
Study Completion Date: June 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Nordihydroguaiaretic Acid (NDGA)
NDGA 2000mg daily

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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:

    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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00678015

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Insmed
  More Information

Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00678015     History of Changes
Other Study ID Numbers: 075511
Study First Received: May 12, 2008
Results First Received: January 28, 2014
Last Updated: March 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
NDGA
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Nordihydroguaiaretic Acid
Lipoxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antioxidants
Protective Agents
Physiological Effects of Drugs
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Therapeutic Uses
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 22, 2014