Phase 2 Efficacy and Pharmacodynamic Study of 2-Methoxyestradiol Nanocrystal Colloidal Dispersion(Panzem® NCD) in Patients With Taxane-Refractory, Metastatic,Hormone-Refractory Prostate Cancer
1. Patients (pts) must have histologically or cytologically confirmed adenocarcinoma of
2. Pts must have evidence of progressive metastatic disease (e.g., new lesions on bone
scan or new/enlarging lesions on computerized tomography [CT] scan) or known
metastatic disease and rising PSA, during or after treatment with a taxane-based
regimen (as well as any other subsequent non-cytotoxic therapy).
- Pts with bone metastases only (i.e., lacking soft-tissue disease) must have a
PSA level of 10 ng/mL or higher.
- Pts with soft tissue metastases and/or visceral disease must have either
measurable disease (per RECIST criteria) or a PSA level of 10 ng/mL or higher.
- For pts with stable metastatic disease and rising PSA: two consecutive rises in
PSA measurement are necessary, each separated from the previous by a minimum of
two weeks. The most recent PSA value must be obtained within 1 week prior to
- At least 3 PSA values within 6 months of registration (each separated by at
least 2 weeks) using the same clinical laboratory needs to be available for
calculation of the PSA pre-treatment slope. Only those values obtained after
the last treatment date (see inclusion criteria #5 below) will be acceptable.
3. Pts must have had prior treatment with bilateral orchiectomy or other primary
hormonal therapy with evidence of treatment failure.
- Pts who have not undergone bilateral orchiectomy must continue their luteinizing
hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin)
or LHRH antagonist (e.g. abarelix) while receiving protocol therapy.
- A serum testosterone level of 50 ng/dL or lower is required to confirm
castration status within 4 weeks prior to study entry.
4. For pts previously treated with flutamide (Eulixin), Nilutamide (Nilandron), or
bicalutamide (Casodex): pts must have discontinued flutamide 4 weeks or more prior to
registration with continued evidence of progressive disease. For bicalutamide or
nilutamide, pts must have discontinued the drug 6 weeks or more prior to registration
with evidence of progressive disease.
• Disease progression following anti-androgen withdrawal needs to be confirmed by a
rising PSA after the required 4-6 week washout period (e.g. PSA level higher than the
last PSA obtained while on anti-androgen therapy).
5. Pts must have received only one prior taxane-based regimen for metastatic disease,
with evidence of disease progression (inclusion criteria #2) during treatment or
within 6 months of treatment discontinuation. Up to one other prior experimental
therapy (non-cytotoxic) is permitted. At least 4 weeks or more from previous
treatment must have elapsed prior to registration, with evidence for disease
progression as outlined in inclusion criteria #2.
6. Age ≥18 years.
7. Life expectancy of greater than 12 weeks.
8. Eastern Cooperative Oncology Group [ECOG] performance status of 2 or less
9. Pts must have near normal organ and marrow function within 2 weeks prior to
registration as defined below:
- Granulocytes > 1500/mm³
- Platelet count > 100,000/mm³
- Bilirubin < 1.5 mg/dL
- Serum glutamate pyruvate transaminase (ALT) < 2 times the institutional upper
limit of normal
- Creatinine < 1.5 mg/dL or a calculated creatinine clearance > 50 mL/min
10. Pts with a history of prior malignancy are eligible provided they were treated with
curative intent and have been free of disease for 5 years or more (excluding
non-melanomatous skin cancers treated with curative intent).
11. All sites of disease must be evaluated within 4 weeks prior to registration.
12. Have the ability to understand the requirements of the study, provide written
informed consent and authorization for release of protected health information, abide
by the study restrictions, and agree to return for the required assessments.
1. The use of bisphosphonates (i.e. pamidronate sodium or zoledronic acid) will be
allowed provided that the patient has been receiving that medication for 4 weeks or
more with evidence of progressive disease as outlined above.
• Pts will not be allowed to start bisphosphonate while receiving protocol treatment
unless clinically indicated (will need approval of the study principal investigator).
Those patients already on a bisphosphonate will need to continue to receive the
bisphosphonate as previously scheduled.
2. Pts must not have had prior radiotherapy within 4 weeks prior to registration.
Patient cannot have had prior Strontium 89, Samarium 153, or other radioisotope.
• If a pt requires palliative radiotherapy, two consecutive rises (baseline value
must be obtained after completion of radiation treatment) in PSA measurement are
necessary, each separated from the previous by a minimum of two weeks.
3. No concurrent use of estrogen, or estrogen-like agents (i.e. PC-SPES, Saw Palmetto,
or other herbal products which may contain phytoestrogens), or any other hormonal
therapy (including megastrol acetate, finasteride, ketoconazole, and systemic
corticosteroids) is allowed at any time during the study. Prior use of these agents
will need to be discontinued 4 weeks or more prior to enrollment. Disease progression
needs to be confirmed as outlined in inclusion criteria #2.
4. Pts with type I insulin-dependent diabetes or poorly-controlled type II
insulin-dependent diabetes or a fasting blood glucose of more than 10 mmol/L (200
mg/dL) will be excluded due to difficulty evaluating the tumor metabolic activity
5. Patients must not have active angina pectoris, or known heart disease of New York
Heart Association Class III-IV. Patients must not have a history of myocardial
infarction within 6 months prior to registration. No history or evidence of
ventricular dysrhythmias or other unstable arrythmia is allowed (rate controlled
atrial fibrillation is allowed if the patient is asymptomatic from a cardiac
6. Patients must not have any known history of carcinomatous meningitis or brain
7. No serious concurrent medical illness or active infection should be present which
would jeopardize the ability of the patient to receive the therapy outlined in this
protocol with reasonable safety.
8. No major surgery within 21 days of starting treatment with Panzem NCD.
9. Pts must not receive any investigational agents other than Panzem NCD for the
duration of their participation in this trial.