177Lu Radiolabeled Monoclonal Antibody HuJ591 (177Lu-J591) and Ketoconazole in Patients With Prostate Cancer

This research is being done because the standard treatments for prostate cancer that has
returned (PSA is elevated) after surgery and/or radiation and progressed on initial hormonal
therapy are not curative. Existing treatments, such as the ketoconazole used as part of this
study may decrease PSA temporarily, but unfortunately the cancer continues to grow. This
experimental drug is designed to seek out all of the prostate cancer cells and to deliver a
lethal dose of radiation to the areas of cancer, but not to normal areas. Some of the normal
organs (liver, kidney and bone marrow) do receive some radiation dose that is within the
acceptable limits.

The experimental drug in this study includes an antibody (abbreviated: mAb) called "J591". It
is a protein molecule which can bind to a specific site on a prostate cancer cell. A very
energetic radioactive (an unstable atom) metal called 177Lutetium (abbreviated: 177Lu) is
attached to the J591 antibody. The fully assembled drug is called "177Lu-J591". The study
will assess the potential of the energy given off by the radioactive compound to kill cancer
cell. This study may also involve the use of 111Indium (abbreviated 111In). This is also an
energetic radioactive particle, but does not generally give off enough energy to kill cancer
cells, but allows researchers to take pictures. This radioactive particle is also attached to
the J591 antibody (called 111In-J591) and will serve as a placebo (treatment with no active
medicine).

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the prostate previously
treated with surgery and/or radiotherapy.

- Biochemical progression (rising PSA) after medical or surgical castration

- High risk of systemic progression defined as:

1. Rising PSA as defined above and either:

2. Absolute PSA > 20 ng/mL AND/OR

3. PSA doubling time < 8 months

- No evidence of local recurrence or distant metastases

- Age >18 years.

- Serum testosterone < 50 ng/ml

- Patients capable of fathering children must agree to use an effective method of
contraception for the duration of the trial.

- Subjects on bisphosphonate therapy must be on a stable dose and must have started
therapy > 4 weeks prior to protocol therapy.

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

Exclusion Criteria:

- Use of red blood cell or platelet transfusions within 4 weeks of treatment

- Use of hematopoietic growth factors within 4 weeks of treatment

- Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment

- Prior radiation therapy encompassing >25% of skeleton

- Prior treatment with 89-Strontium or 153-Samarium containing compounds (e.g.
Metastron®, Quadramet®)

- Platelet count <150,000/mm3

- Absolute neutrophil count (ANC) <2,000/mm3

- Hematocrit <30 percent or Hemoglobin < 10 g/dL

- Abnormal coagulation profile (PT or INR, PTT) > 1.3x ULN

- Serum creatinine >2.5 mg/dL

- AST (SGOT) >2x ULN

- Bilirubin (total) >1.5x ULN

- Serum calcium >11 mg/dL

- Active serious infection

- Active angina pectoris or NY Heart Association Class III-IV

- Karnofsky Performance Status <70

- Life expectancy <12 months

- History of deep vein thrombosis and/or pulmonary embolus within 3 months of study
entry

- Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or
hematological organ systems which might preclude completion of this study or interfere
with determination of causality of any adverse effects experienced in this study.

- Prior investigational therapy (medications or devices) within 6 weeks of treatment.

- Prior use of ketoconazole for the purposes of prostate cancer therapy

- Known history of HIV.

- Currently active other malignancy other than non-melanoma skin cancer.