PS-341 Followed by Removal of Prostate for Those With Prostate Cancer
Condition: Prostate Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: PS-341 (bortezomib)
Intervention description: PS-341 is a dipeptidyl boronic acid inhibitor with high specificity for the proteasome developed by Millennium Pharmaceuticals Inc. to treat human malignancies. It is the first member of this class of anti-tumor agents to come to human trials. Patients will receive PS-341 (1.6mg/m2/dose) by intravenous push weekly for 4 consecutive weeks followed by a 24-72 hour rest. This schedule consists of one treatment cycle. Upon the completion of 4 weeks of PS-341 followed by a 24-72 hour rest period, radical prostatectomy will be performed.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate Cancer; Bortezomib; Radical Prostatectomy; Phase 2 Clinical Trial

Summary:

      Following pretreatment evaluation, patients receive PS-341 by intravenous push weekly for 4
      consecutive weeks followed by a 24-72 hour rest period. This schedule consists of one
      treatment cycle. Upon the completion of 4 weeks of PS-341 followed by a 24-72 hour rest
      period, radical prostatectomy will be performed. Surgery will be delayed if there is any
      bleeding abnormality (bleeding time greater than 10 minutes) and until platelet count is more
      than or equal to 100,000 and coagulation profile (PT, PTT) is normal. If at the time of
      surgery a patient is found to have positive lymph nodes, prostatectomy will be abandoned, the
      prostate will be biopsied, and the patient will be offered other treatment modalities
      (hormones, radiation therapy).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic proof of prostatic adenocarcinoma without evidence of regional and/or
             distant metastasis, clinical stage T1, T2 or T3 with high grade disease (Gleason's
             grade 7 or above).

          -  Recent (less than or equal to 6 weeks prior to study entry) negative bone scan and CT
             scan of abdomen/pelvis.

          -  Appropriate surgical candidate for radical prostatectomy and a performance status of
             less than or equal to 2 (Zubrod scale).

          -  Patients should have adequate bone marrow function defined as an absolute peripheral
             granulocyte count greater than or equal to 1,500 and platelet count of greater than or
             equal to 100,000, adequate hepatic function with a bilirubin less than or equal to 1.5
             mg % and SGPT less than 2.5x the upper limits of normal, adequate renal function
             defined as serum creatinine less than or equal to 2.0 mg %.

          -  Patients must have normal coagulation profile (PT, PTT) and no history of substantial
             non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only
             (for control of central line patency).

          -  Patients must sign an informed consent indicating that they are aware of the
             investigational nature of the study, in keeping with the policies of the institution.

          -  Patients screened and found eligible for the study, but not wanting to participate for
             any reason, will be followed along with the patients enrolled in the study in an
             effort to obtain outcome information (as historical information for design of future
             trials).

          -  No evidence of bifascicular block or active ischemia on EKG.

          -  Patients must have no history of congestive heart failure or previous MI.

        Exclusion Criteria:

          -  Previous or current hormonal treatment, chemotherapy, radiation therapy, immunotherapy
             or other investigational status drug.

          -  Unable to tolerate transrectal ultrasound.

          -  Patients who are not appropriate surgical candidates for radical prostatectomy based
             on the evaluation of co-existent medical diseases and competing causes of death.
             Patients with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorder
             are not eligible.

          -  Patients who are HIV positive or have chronic hepatitis B or C infections are not
             eligible.

          -  Patients on steroid medications are not eligible.

          -  Patients with uncontrolled and symptomatic orthostatic hypotension or uncontrolled
             hypertension are not eligible.

          -  Patients with significant arteriosclerotic disease, as defined by a previous arterial
             bypass, claudication limiting activity, or a history of cerebrovascular events within
             the last year (including TIA) are not eligible.

          -  Patients with diabetes mellitus requiring insulin or oral hypoglycemics for more than
             5 years are not eligible.

          -  Patient has greater than or equal to grade 1 peripheral neuropathy within 14 days
             before enrollment.

          -  Hypersensitivity to boron, mannitol, or bortezomib.