A Phase I Study Of Combination Neoadjuvant Hormone Therapy And Weekly OGX-011 (Clusterin Antisense Oligonucleotide) Prior To Radical Prostatectomy In Patients With Localized Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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:
- •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:
- •Performance status
- •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
- •Bilirubin normal
- •AST and ALT normal
- •PTT normal
- •INR normal
- •Creatinine normal
- •Cardiovascular
- •No significant cardiac dysfunction
- •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
- •Not specified
- •No concurrent heparin or warfarin anticoagulation
- •No other concurrent investigational therapy
- •No other concurrent cytotoxic therapy
排除标准
- 未提供