A Phase II Trial of Phenoxodiol in Patients With Castrate and Non-Castrate Prostate Cancer

Inclusion Criteria:

- All patients must have histologically or cytologically confirmed adenocarcinoma of
the prostate

- Patients with castrate and non-castrate levels of testosterone are eligible as
defined below.

- Patients with castrate level of testosterone (Group A- androgen independent disease)
need to meet the following criteria:

- Progressive disease based on any one of the following

a) a rise in PSA, b) transaxial imaging, or c) radionuclide bone scan. Patients
whose sole manifestation of progression is an increase in disease related symptoms
are not eligible.

1. PSA - a minimum of 3 consecutive rising levels, with an interval of > 1 week
between each determination. The last determination must have a minimal value of
> 4 ng/ml and be determined within two weeks prior to registration.

2. Measurable Disease: Patient showing new or progressive soft tissue masses on CT
or MRI scans are eligible.

3. Radionuclide bone scan: New metastatic lesions.

- Serum testosterone < 50 ng/ml, determined within two weeks prior to starting
treatment

- Maintaining castrate status: Patients who have not undergone surgical orchiectomy
should continue on medical therapies [i.e. gonadotropin releasing hormone analogs
(GnRH analogs) to maintain castrate levels of serum testosterone. Patients who are
receiving an anti-androgen as part of their first-line hormonal therapy must have
shown progression of disease off of the anti-androgen prior to enrollment. Patients
must discontinue Megestrol Acetate (MEGACE) and show progression of disease off of
this medication.

- No prior chemotherapy except for adjuvant or neo-adjuvant therapy given > than 3
years prior to enrollment

- No more than one prior course of palliative radiotherapy. No prior radioisotope
therapy with Strontium-89 or Samarium.

- Patients with non-castrate levels of testosterone (Group B- androgen dependent
disease) need to meet the following criteria:

- A rising PSA after radical prostatectomy, radiotherapy or radiation implants with no
evidence of metastatic disease on bone, CT scan or MRI scan.

- PSA doubling time less than 12 months

- Testosterone level > 50 ng/ml

- Age > 18 years of age.

- Karnofsky Performance Status > 70%

- Four weeks since major surgery.

- Patients must have signed an informed consent document stating that they understand
the investigational nature of the proposed treatment.

- Required Initial Laboratory Data:

- WBC > 3,000/µl

- ANC > 1,500/µl

- Hemoglobin > 9 g/dl

- Platelet count > 100,000/µl

- Creatinine < 1.5 x upper limits of normal

- Bilirubin within 2 x normal limits

- SGOT (AST) < 2.5 x upper limits of normal

- SGPT (AST) < 2.5 x upper limits of normal

- PSA > 4.0 ng/ml (if no measurable disease for Group B) > 4.0 ng/ml for Group A

- PT within normal limits(*)

- PTT within normal limits(*)

(*)unless patients are already anti-coagulated for other reasons (i.e. atrial
fibrillation, etc.)

- Agree to use adequate contraception (hormonal or barrier method of birth control)
prior to study entry and for the duration of study participation and for additional 1
months after finishing Phenoxodiol.

- Able to swallow and retain oral medication

- Life expectancy >3 months

Exclusion Criteria:

- Patients may not be receiving any other investigational agents.

- Patients may continue on a daily Multi-Vitamin and Calcium supplements but all other
herbal, alternative and food supplements (i.e. PC-Spes, Saw Palmetto, St John Wort,
etc.) must be discontinued before registration.

- Bisphosphonate therapy for bone metastases is allowed; however, treatment must be
initiated prior to the first dose of PXD. Prophylactic use of bisphosphonates in
patients without bone disease, except for the treatment of osteoporosis, and
initiation of bisphosphonates during study treatment is not permitted.

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.

- Patients with significant cardiovascular disease including congestive heart failure
(New York Heart Association Class III or IV), active angina pectoris or recent
myocardial infarction (within the last 6 months) are excluded.

- Patients with prior history of hemorrhagic or thrombotic cerebral vascular accident,
deep venous thrombosis or pulmonary embolism within the past 6 months are excluded.

- Patients with a "currently active" second malignancy other than non-melanoma skin
cancers are not to be registered. Patients are not considered to have a "currently
active" malignancy if they have completed therapy and are now considered (by their
physician) to be at less than 30% risk for relapse.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Because patients with immune deficiency are at increased risk of lethal infections
when treated with marrow-suppressive therapy, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with Phenoxodiol. Appropriate studies will be undertaken
in patients receiving combination anti-retroviral therapy when indicated.