Treatment of patients with Androgen-Independent Prostate Carcinoma who progressed on or after prior chemotherapy.
Conditions
Interventions
Trade Name: VELCADE
Product Name: VELCADE 3.5mg powder for solution for injection
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Bortezomib
CAS Number: 179324-69-7
Other d
Sponsors
Christos N. Papandreou
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1 Signed informed consent. 2 Histologic demonstration of adenocarcinoma of the prostate. If no sample of the primary tumor was obtained, biopsy of a metastatic site is sufficient if the tissue stains positive for PSA. 3 Androgen-Independent progression of prostate carcinoma, as shown by: Serum testosterone level of 50%. 11 ALT and AST ?2.5 ? the ULN, or, if the patient has liver metastases, ?5 ? the ULN. 12 Total bilirubin ?1.5 ?the upper limit of normal (ULN). 13 Serum creatinine 2 mg/dl, then a creatinine clearance of at least 35 ml/min (measured or estimated by the Cockroft formula: CLcr= [(140-age)
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study. 1 Patient has never received chemotherapy for prostate carcinoma or has received chemotherapy within four weeks (six weeks for nitrosoureas) or antibody therapy within eight weeks of enrollment. 2 Patient has received radiation therapy or Samarium-153 within four weeks of enrollment, or Strontium-89 within 12 weeks of enrollment. 3 Patient has not recovered from all serious toxic effects of previous chemotherapy or radiation or antibody therapy. 4 Patient received treatment with flutamide within four weeks of enrollment or nilutamide or bicalutamide within six weeks of enrollment and there is no evidence of disease progression since discontinuation of the anti-androgen. 5 Patient has had any major surgery within four weeks of enrollment. 6 Patient has significant atherosclerotic disease, as defined by: a) myocardial infarction within six months of enrollment, uncontrolled / unstable angina pectoris or electrocardiographic evidence of acute ischemia b) clinically significant ventricular arrhythmias, c) symptomatic congestive heart failure d) significant conduction abnormalities: 2nd or 3rd degree AV blocks, bifascicular block (defined as Left Anterior Hemiblock in the presence of Right Bundle Branch Block), e) claudication limiting activity and f) history of cerebrovascular events within the last year -including transient ischemic attack (TIA) 7 Patient has uncontrolled and symptomatic orthostatic hypotension or uncontrolled hypertension. 8 Patient has uncontrolled brain metastases or central nervous system disease. 9 Patient has ? Grade 2 peripheral neuropathy or neuropathic pain (per NCI CTCAE v.3.0, Attachment 7). 10 Patient has an uncontrolled inter-current illness (e.g., active infection). 11 Patients with a history of another malignancy (except from superficial bladder cancer or basal cell carcinoma of the skin) within 5 years prior to study entry. 12 Patient has another serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the patient’s ability to provide informed consent or with the completion of treatment according to this protocol. 13 History of allergic reaction attributable to compounds containing boron or mannitol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of VELCADE (bortezomib) in patients with metastatic Androgen-Independent Prostate Cancer (AIPCa) progressing on or after prior chemotherapy, as measured by the objective response rate and PSA response rate of the treatment in patients with AI-PCa who failed up to two prior chemotherapy regimens. To evaluate the toxicity of the treatment in patients with metastatic AI-PCa progressing after chemotherapy. ;Secondary Objective: Investigate the degree of proteasome inhibition in peripheral blood in patients with advanced androgen-independent prostate cancer who are receiving VELCADE. Evaluate the effect of VELCADE (bortezomib) on prostate-specific antigen (PSA) levels in patients with baseline PSA levels ?5 ng/mL and correlate with the degree of proteasomal inhibition in blood. Assess serum IL-6 levels (as a surrogate of NF?B activation) and investigate the relationship between serum interleukin-6, serum PSA levels and peripheral blood proteasomal inhibition in patients with advanced androgen-independent prostate cancer. Monitor the effect of VELCADE (bortezomib) on selected parameters of clinical benefitCollect and store plasma, urine and tissue samples (i.e. prostate, bone marrow and / or lymph node) from consenting patients (optional procedures) for future studies (i.e., study the effect of the therapy on known targets of NF?B, growth factors for prostate cancer, and bone remodeling markers). ;Primary end point(s): Evaluate the efficacy of VELCADE (bortezomib) in patients with metastatic Androgen-Independent Prostate Cancer (AIPCa) progressing on or after prior chemotherapy, as measured by the objective response rate and PSA response rate of the treatment in patients with AI-PCa who failed up to two prior chemotherapy regimens. To evaluate the toxicity of the treatment in patients with metastatic AI-PCa progressing after chemotherapy. | — |
Countries
Greece
Outcome results
None listed