phase i/ii dose escalation study of velcade® and docetaxel in patients with advanced androgen-independent prostate cancer

Conditions: Prostatic Neoplasms

Summary: 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.

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.

Eligibility 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.

Keywords: advanced androgen-independent prostate cancer