The purpose of this study is to evaluate how safe PS-341(VELCADE) is when given with Docetaxel (Taxotere) to patients with androgen-independent prostate cancer, and also to see what effects (good and bad) it has on you and on your cancer.

Condition	Treatment or Intervention	Phase
Prostatic Neoplasms	Drug: VELCADE TM (bortezomib) for Injection	Phase I Phase II

Further Study Details: 

Expected Total Enrollment:  102

This is a dose escalation study, which means that the first group of patients will receive a low dose of PS-341 (VELCADE) and Docetaxel (Taxotere). If the low dose of VELCADE and Taxotere appears to be safe, then the next group of patients will receive a higher dose of VELCADE and Taxotere.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Male

Criteria

Inclusion criteria Each patient must meet all of the following inclusion criteria to be enrolled in the study:

• Patient has histologically-confirmed advanced and/or metastatic androgen-independent prostate cancer requiring anti-neoplastic treatment.
• Previous or concurrent hormone therapy with a luteinizing hormone-releasing hormone analog (e.g., leuprolide) does not preclude enrollment in the study.
• Patient has progressive measurable or evaluable disease, defined as meeting at least one of the following three criteria [1]: 1.Progressive measurable disease (changes in the size of lymph nodes or parenchymal masses on physical examination or x-ray). 2.Progressive bone metastasis [presence of new lesion(s) on a bone scan]. 3.Progressive PSA, as evidenced by two separate measurements taken at least one week apart and confirmed by a third, and if necessary, a fourth measurement.
• If the third measurement is not greater than the second measurement, then a fourth measurement must be taken; the fourth measurement must be greater than the second measurement for the patient to be eligible for enrollment in the study.
• The confirmatory PSA measurement (i.e., the third or, if applicable, fourth PSA measurement) must be greater than or equal to 5 ng/mL.
• Patient is 18 years of age or older.
• Patient has a Karnofsky performance status of 60% or greater.
• Patient has a life expectancy of three months or longer.
• Patient has all of the following pretreatment laboratory data within 14 days before the first study drug dose:
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3.
• Platelets greater than or equal to100,000/mm3.
• Hemoglobin >8.0 g/dL.
• Serum creatinine less than or equal to 2.5 mg/dL.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care.
• Patient agrees to use an acceptable barrier method for contraception from Screening through 90 days after the last study drug dose. [It is recommended that female partners of male patients enrolled in this study also use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence).]

Exclusion criteria Patients meeting any of the following exclusion criteria are not to be enrolled in the study.

• Patient has received chemotherapy within four weeks, nitrosoureas within six weeks, or antibody therapy within eight weeks of enrollment.
• Patient has received radiation therapy within four weeks of enrollment.
• Patient has not recovered from all toxic effects of previous chemotherapy or radiation or antibody therapy.
• Patient received treatment with flutamide within four weeks of enrollment or nilutamide or bicalutamide within six weeks of enrollment.
• Patient has had any major surgery within four weeks of enrollment.
• Patient has a history of allergic reactions to diuretics or anti-emetics suggested to be administered in conjunction with study drug
• Patient has a history of severe hypersensitivity reaction to docetaxel or other agents formulated with polysorbate 80.
• Patient had a myocardial infarction within six months of enrollment or has uncontrolled angina, severe uncontrolled ventricular arrhythmias, symptomatic congestive heart failure, unstable angina pectoris, or electrocardiographic evidence of acute ischemia
• Patient has uncontrolled brain metastases or central nervous system disease.
• Patient has Grade 2 or higher peripheral neuropathy
• Patient has any of the following pretreatment laboratory data within 14 days before the first study drug dose:
• Total bilirubin > than the upper limit of normal (ULN).
• Alanine transaminase (ALT) and/or aspartate transaminase (AST) >1.5 x the ULN concurrent with alkaline phosphatase >2.5 x the ULN.
• Alkaline phosphatase >5 x the ULN, unless shown by fractionation to be bone-derived and AST, ALT, bilirubin, gamma glutamyl transferase (GGT), and 5'nucleotidase are <1.5 x the ULN and bilirubin is within normal range.
• Serum testosterone 50 ng/mL or higher.
• Patient is HIV-infected.
• Patient is hepatitis B surface antigen positive or has previously documented hepatitis C infection.
• Patient has an uncontrolled intercurrent illness (e.g., active infection).
• Patient has another serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.

California
      Cedars Sinai Medical Center, Los Angeles,  California,  90048,  United States
New York
      Columbia-Presbyterian Hospital, New York,  New York,  10032,  United States
Ohio
      Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States
Tennessee
      Vanderbilt University Medical Center, Nashville,  Tennessee,  37232,  United States

Study ID Numbers:  M34101-033
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  July 10, 2003
ClinicalTrials.gov Identifier:  NCT00064610
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08