A Phase II, Open-Label, Randomized Trial of Zoledronic Acid (Zometa™) and BMS-275291 (NSC#713763) in Patients With Hormone Refractory Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Confirmed response (PSA decline of greater than 50% confirmed at least four weeks apart)
研究概览
简要总结
Phase II trial to study the effectiveness of combining zoledronate with BMS-275291 in treating patients who have prostate cancer that has not responded to previous hormone therapy. Zoledronate may prevent bone loss and stop the growth of tumor cells in bone. BMS-275291 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Combining zoledronate with BMS-275291 may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the confirmed response rate of hormone refractory prostate cancer patients treated with Zometa with BMS-275291.
SECONDARY OBJECTIVES:
I. To evaluate the toxicity profile associated with this treatment in this patient population.
II. To evaluate the overall and progression-free survival associated with this treatment regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed (adeno)carcinoma of the prostate refractory to hormone therapy
- •Metastatic bone disease, as documented by bone scan and confirmed by x-rays, CT scan or MRI scan
- •Note: Patients may also have measurable disease in the lymph nodes (retroperitoneal, pelvic or inguinal only), prostate and /or prostatic bed; measurable disease is defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm =< 21 days prior to registration
- •PSA progression defined as two consecutive increases in PSA value over the previous reference value; the first increase of PSA should occur no earlier than one (1) week after the reference measurement; all patients need to demonstrate continued PSA elevation with an increasing PSA four weeks after the required cessation of their antiandrogen treatment; the required cessation period is 4 weeks for flutamide, nilutamide, and Megace-based treatment, and 8 weeks for bicalutamide-based treatment
- •One of the following:
- •Continuing primary androgen suppression (LHRH agonist)
- •Orchiectomy
- •WBC >= 2000/mm^3
- •Absolute neutrophil count (ANC) >= 1500/mm^3
- •PLT >= 100,000/mm^3
- •Hgb >= 9.0 g/dL
- •Total bilirubin =< institutional upper normal limits (UNL)
- •AST =< 1.5 x UNL
- •Serum creatinine =< 1.5 x UNL
- •PSA >= 5 ng/mL
- •Serum testosterone < 50 ng/dL =< 3 months prior to registration
- •Estimated life expectancy of >= 6 months
- •ECOG Performance Status (PS) 0, 1, or 2
- •Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent
- •If sexually active, willing to use an accepted and effective method of contraception consistently for the duration of study participation
排除标准
- •Any of the following:
- •> 2 prior chemotherapy regimen
- •> 2 non-hormonal treatments for metastatic disease (including biologics, gene therapy, angiogenesis inhibitors, etc., but excluding external radiotherapy)
- •Prior therapy with a matrix metalloproteinase inhibitor (MMPI)
- •Immunotherapy =< 4 weeks prior to study entry
- •Biologic therapy =< 4 weeks prior to study entry
- •Radiation therapy =< 4 weeks prior to study entry
- •Concomitant hormonal treatment (except LHRH)
- •Prior use of systemic radiopharmaceuticals such as samarium and strontium
- •PC-Spes =< 4 weeks prior to study entry
- •Failure to fully recover from adverse effects of prior therapies regardless of interval since last treatment
- •Other concurrent chemotherapy, immunotherapy, or radiotherapy directed at the cancer
- •Other therapy or supportive care that is considered investigational
- •Known CNS metastases
- •Known visceral metastases (pulmonary, liver, kidney, splenic lesions); patients with retroperitoneal, pelvic or inguinal lymph node metastases and/or disease in the prostate (or prostatic bed) will not be excluded
- •Uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris, cardiac arrhythmia
- •Psychiatric illness/social situations that would limit compliance with study requirements
- •HIV-positive patients receiving combination anti-retroviral therapy
- •Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancer from which the patient has been disease free for >= 5 years
研究组 & 干预措施
Arm I (rebimastat, zoledronic acid)
Patients receive zoledronate IV over at least 15 minutes on day 1 and oral BMS-275291 daily on days 1-28.
干预措施: rebimastat (Drug)
Arm I (rebimastat, zoledronic acid)
Patients receive zoledronate IV over at least 15 minutes on day 1 and oral BMS-275291 daily on days 1-28.
干预措施: zoledronic acid (Drug)
Arm I (rebimastat, zoledronic acid)
Patients receive zoledronate IV over at least 15 minutes on day 1 and oral BMS-275291 daily on days 1-28.
干预措施: laboratory biomarker analysis (Other)
Arm II (zoledronic acid)
Patients receive zoledronate as in Arm I.
干预措施: zoledronic acid (Drug)
Arm II (zoledronic acid)
Patients receive zoledronate as in Arm I.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Confirmed response (PSA decline of greater than 50% confirmed at least four weeks apart)
时间窗: Up to 2 years
次要结局
- Overall survival time(From registration to death due to any cause, assessed for up to 2 years)
- Time to disease progression(From registration to documentation of disease progression, assessed up to 2 years)
- Duration of PSA response or duration of PSA control(Up to 2 years)
- Incidence of toxicity as per NCI CTCAE version 2.0(Up to 2 years)