Exogenous Testosterone Plus Dutasteride for the Treatment of Castrate Metastatic Prostate Cancer

Inclusion Criteria:

- Patients should have histologically confirmed castration-resistant metastatic
prostate cancer with evidence of disease progression. Patients must have been in a
castrate state either by orchiectomy or by GnRH analogues for a minimum of one year.
In detail, they should meet all of the following criteria:

- Adult male > or = to 18 years of age

- Histologically confirmed prostate cancer, currently with progressive disease, defined
as rising PSA (50% or more increase to a level of 2 ng/mL or more, based on at least
3 PSA determinations obtained at least 1 weeks apart), or 2 new osseous lesions by
bone scan, soft tissue disease progression by RECIST 1.1 criteria , or the appearance
of new sites of disease (by MRI/CT).

- Evidence of metastatic disease, documented within 4 weeks prior to dutasteride
treatment initiation, based on a:

- CT or MRI of the abdomen and pelvis, and/or

- Radionuclide bone scan (in case of findings suspicious for spinal metastasis,
MRI of the spine will be performed to rule out epidural disease)

- Serum PSA ≥ 2 ng/mL within 4 weeks prior to dutasteride treatment initiation in order
to register to the protocol

- Normal organ function with acceptable initial laboratory values documented within 4
weeks prior to dutasteride treatment initiation:

- WBC > or = to 3000/µL

- Platelets > or = to 100,000/µL

- Creatinine < or = to 2 mg/dL

- Bilirubin < or = to 1.5 X ULN (institutional upper limits of normal)

- AST/ALT < or = to 2 X ULN

- Karnofsky performance status > or = to 70%

- Willingness to undergo serial blood draws for the purpose of measuring CTCs and other
biomarkers. MSKCC patients will need to agree to participate in MSKCC protocol 90-040
Molecular studies and clinical correlations in human prostate cancer [PI: Scher].
Also, MSKCC patients will undergo serial imaging by FDHT and FDG PET scans, under
protocol 00-095 [18f]-fluoro-2-deoxy-D-glucose and [18f]-dihydro-testosterone PET
imaging in patients with progressive prostate cancer (PI: Morris), depending on
tracer and scanner time availability. If the study is opened in other centers outside
MSKCC, those centers will be exempt from procedures linked to the MSKCC Protocol #
00-095.

- ADT treatment for at least 12 months prior to study entry with serum testosterone <
50 ng/dL.

- Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- Patients meeting any of the following criteria will not be eligible for study entry:

- Evidence of small-cell or neuroendocrine pathologic features

- Uncontrolled urinary obstruction

- Osseous metastatic disease with imminent risk (at the discretion of the treating
physician) of pathologic fracture or cord compression (in patients with known spinal
metastasis raising concern for cord compression, MRI of the spine should be performed
to rule out epidural disease)

- Any situation where, at the discretion of the treating physician, a potential "tumor
flare" would be life-threatening

- Sleep apnea (unless under good control with current treatment)

- Polycythemia vera

- History of allergic reactions attributed to compounds of similar chemical or
biological composition to dutasteride

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

- Currently active secondary malignancy (as determined by the treating physician) other
than non-melanoma skin cancer

- Use of the following medications will be prohibited during the study:

- Current and/or previous use of the following medications:

- Finasteride (Proscar, Propecia) or dutasteride (GI198745, Avodart) exposure
within 6 months of study entry.

- Anabolic androgenic steroids, including but not limited to testosterone, 17β
testosterone esters, methyltestosterone, stanozolol, and danazol (within 6
months of study entry). Corticosteroids, including hydrocortisone, dexamethasone
and prednisone are acceptable.

- Additional hormonal therapy within 4 weeks of study entry:

- Including megestrol, medroxyprogesterone, cyproterone, and DES

- Drugs with antiandrogenic properties (eg, spironolactone if > 50mg/d, flutamide,
bicalutamide, nilutamide, ketoconazole,* progestational agents) * Includes
topical ketoconazole.

- Evidence of epidural disease by MRI