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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00678015
• Other study ID #: 075511
• Status: Terminated
• Phase: Phase 2
• First received: May 12, 2008
• Last updated: March 11, 2014
• Start date: May 2008
• Est. completion date: June 2011

Study information

• Verified date: March 2014
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: June 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Nordihydroguaiaretic Acid (NDGA)
NDGA 2000mg daily

Locations

Country	Name	City	State
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Insmed Incorporated

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 prost — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Monthly, up to 29 months	No