Study of Abarelix in Androgen-Independent Prostate Cancer Progressing After Agonist Therapy

Inclusion Criteria:

Signed informed consent

Histologically or cytologically confirmed prostate cancer that has progressed within 60 days of the start of screening despite castrate levels of testosterone from treatment with an LHRH agonist. Progression will be defined as one or more of the following: *A rising PSA, defined as at least two consecutive rises in PSA over a reference value (PSA #1). The first rising PSA (PSA #2) must be taken at least one week after PSA #1. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2, OR

The appearance of new metastatic lesions on a bone scan, OR
Progression of known lesions or the appearance of new metastatic lesions on CT, MRI, chest x-ray, or other radiographic evaluations.
Subject whose hormonal therapy includes an anti-androgen must have the anti-androgen discontinued prior to the start of screening (at least 6 weeks for bicalutamide and at least 4 weeks otherwise). If there is a reduction in the PSA after anti-androgen withdrawal, the subject must continue to demonstrate progression as defined above after anti- androgen withdrawal to be eligible.
ECOG Performance Status ≤ 3
Age ≥ 18 years of age
Life expectancy ≥ 6 months
Serum testosterone less than or equal to 50 ng/dL
PSA ≥ 5 ng/mL (if progression is determined from a rise in PSA)
WBC greater than or equal to 3,000/mm3
Hematocrit ≥ 30%
Platelet count greater than or equal to 100,000/mm3
Serum creatinine less than or equal to 2 x upper limit of normal (ULN)
Bilirubin (direct or total) less than or equal to 2 x ULN
SGPT (ALT) and SGOT (AST) less than or equal to 2 x ULN

Exclusion Criteria:

A subject is ineligible to participate in the study if he meets any of the following criteria:

Prior treatment for prostate cancer with:

Chemotherapy
Radiopharmaceutical such as strontium or samarium
Diethylstilbesterol or another estrogen agonist or antagonist
Ketoconazole
Aminoglutethimide
Current treatment with Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medication
Currently taking PC SPES
History of allergy to a LHRH agonist or GnRH antagonist
Major surgery within 4 weeks
Serious medical illnesses, including malnutrition, that in the judgment of the investigator would preclude protocol treatment
Significant cardiovascular illness defined as NYHA class III or IV congestive heart failure or unstable angina within 6 months, myocardial infarction within 12 months, deep venous thrombosis within 2 years, or any history of acute pulmonary embolism
Active second malignancy other than non-melanoma skin cancer or superficial bladder cancer
Any uncontrolled infection, including HIV
Any other experimental therapy within 4 weeks prior to study entry
QTc > 450 msec on a screening ECG obtained by the investigator