Per protocol - interim analysis showed no significant PSA declines among the first 12 patients after 3 cycles of treatment

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.

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).

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)

Monthly during study treatment, 2-33 months

Patients were evaluated monthly for toxicity, which was graded according to common toxicity criteria (CTC) 3.0

Per protocol - accrual was stopped early after a pre-planned interim analysis showed no significant PSA declines after 3 cycles of treatment among the first 12 patients enrolled.