Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage III prostate cancer, stage II prostate cancer
Brief summary
RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as flutamide and buserelin may stop the adrenal glands from producing androgens. OGX-011 may help flutamide and buserelin kill more tumor cells by making tumor cells more sensitive to the drugs. Giving flutamide and buserelin with OGX-011 before surgery may shrink the tumor so it can be removed during surgery. PURPOSE: Phase I trial to study the effectiveness of combining hormone therapy with OGX-011 before radical prostatectomy in treating patients who have prostate cancer.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose and recommended phase II dose of OGX-011 (clusterin antisense oligonucleotide) when administered with neoadjuvant hormonal therapy before radical prostatectomy in patients with adenocarcinoma of the prostate. * Determine the toxicity of this regimen in these patients. * Determine the pharmacokinetics of OGX-011 when this regimen is administered in these patients.. * Assess the effects of this regimen on pathologic complete response rates in these patients. * Correlate plasma and/or prostate concentrations of OGX-011 with patient response or toxicity measures. OUTLINE: This is a dose-escalation study of OGX-011. Patients receive OGX-011 IV over 2 hours on days 1, 3, 5, 8, 15, 22, and 29; oral flutamide three times daily for 4 weeks; and buserelin subcutaneously on day 1. Cohorts of 3-6 patients (except for 1 patient at starting dose) receive escalating doses of OGX-011 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose is the dose preceding the MTD. Patients undergo radical prostatectomy and bilateral pelvic lymphadenectomy 1 week after the last dose of neoadjuvant therapy. Patients are followed at 7 days after surgery and then at 3 months. PROJECTED ACCRUAL: Approximately 25-33 patients will be accrued for this study.
Interventions
DRUGbuserelin
DRUGcustirsen sodium
DRUGflutamide
PROCEDUREconventional surgery
PROCEDUREneoadjuvant therapy
Sponsors
NCIC Clinical Trials Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the prostate * High-risk, localized disease that is previously untreated * Minimum of 2 positive biopsies * Meets at least 1 of the following criteria: * Stage T3 * Serum PSA greater than 10 ng/mL * Gleason score 7-10 * Gleason score 6 and at least 3 positive biopsies * Potential candidate for radical prostatectomy PATIENT CHARACTERISTICS: Age * Over 18 Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * WBC at least 3,000/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 10.0 g/dL Hepatic * Bilirubin normal * AST and ALT normal * PTT normal * INR normal Renal * Creatinine normal Cardiovascular * No significant cardiac dysfunction Other * Fertile patients must use effective contraception * No known hypersensitivity to oligonucleotides, luteinizing hormone-releasing hormone analogs, or anti-androgens * No evidence of active uncontrolled infection * No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer * No other serious illness, psychiatric disorder, or medical condition that would preclude study compliance * No history of a significant neurological disorder that would preclude informed consent * No geographical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for prostate cancer Endocrine therapy * No prior hormonal therapy for prostate cancer Radiotherapy * No prior radiotherapy for prostate cancer * No concurrent radiotherapy Surgery * Not specified Other * No concurrent heparin or warfarin anticoagulation * No other concurrent investigational therapy * No other concurrent cytotoxic therapy
Countries
Canada
Outcome results
None listed