A Phase I/II, Open Label, Dose Escalation Study to Determine the Tolerance and Preliminary Activity of PS-341 Plus Docetaxel in Patients With Advanced Androgen-Independent Prostate Cancer Requiring Chemotherapy
Each patient must meet all of the following inclusion criteria to be enrolled in the
- 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. 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.