Phase I/II Study of Docetaxel (Taxotere) in Combination With Doxorubicin HCI Liposome Injection (Doxil) in Advanced Androgen-Independent Prostate Cancer (AIPC)

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed adenocarcinoma of the
prostate.

- Androgen-independent disease progression, as shown by:

- A castrate testosterone level of < 40 ng/dl (this measurement is required only for
patients treated with medical testicular suppression). If testicular suppression is
achieved medically, treatment to maintain castrate levels of testosterone must be
applied continuously.

- A PSA level of at least 4 ng/ml, and rising (with an absolute change of at least 1
ng/ml) on two consecutive measurements at least 2 weeks apart prior to study entry.

- Patients must be off anti-androgens such as flutamide (Eulexin) or nilutamide
(Nilandron) for at least four weeks, and six weeks for bicalutamide (Casodex),
without evidence of response; or have evidence of progression since anti-androgen
withdrawal.

- None or one previous cytotoxic therapy is allowed. (For this study, a combination of
agents given at the same period of time is considered one chemotherapy treatment)

- Age > 18 years of age.

- Life expectancy of greater than 12 weeks.

- ECOG performance status 0, 1 or 2 (Karnofsky >50%; see Appendix B).

- Patients must have adequate bone marrow function as defined below:

- absolute neutrophil count > 1,500/ul

- platelets > 100,000/ul

- hemoglobin > 8 g/dl

- Patients must have adequate liver function as defined below:

- total bilirubin normal, albumin > 3.0 g/dl, and no ascites

- AST(SGOT) and ALT(SGPT) and Alkaline Phosphatase must be within the range
allowing for eligibility

- Patients must have adequate renal function as defined by a creatinine < 2.5 mg/dl or
a creatinine clearance > 30 mL/min (measured or estimated by the Cockroft formula)
for patients with creatinine levels above 2.5 mg/dl

- Patients must have recovered from acute toxicities from chemotherapy or radiotherapy
administered prior to entering this study. Alopecia may not be resolved and
peripheral neuropathy (grade 1) may be present.

- Patients must have a MUGA scan or 2-d echocardiogram indicating an ejection fraction
of > 50% within 42 days prior to first dose of study drug. The method used at
baseline must be used for later monitoring.

- Patients with reproductive potential must use an adequate contraceptive method (e.g.,
abstinence, intrauterine device, oral contraceptives, barrier device with spermicide
or surgical sterilization) during treatment and for three months after completing
treatment.

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

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Patients who have had two or more prior chemotherapy treatment(s) (For this study, a
combination of agents given at the same period of time is considered one chemotherapy
treatment).

- Patients receiving any other investigational agent(s).

- Patients with symptomatic brain metastases or actively receiving any therapy for
brain metastasis (because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events).

- Active second malignancy in the last 5 years except for non-melanoma skin cancer or
carcinoma-in-situ.

- History of cardiac disease, with New York Heart Association Class II or greater, or
clinical evidence of congestive heart failure.

- History of hypersensitivity reactions attributed to a conventional formulation of
doxorubicin HCL, the components of Doxil, docetaxel or other drugs formulated with
polysorbate 80.

- 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.