Phase I Study Of Oral, 1,25 Dihydroxycholecalciferol (Calcitriol) + Dexamethasone In Hormone-refractory Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- MTD of calcitriol (oral, MTW weekly + dexamethasone (oral, Sunday, Monday, Tuesday, Wednesday - SMTW) in men with hormone refractory prostate cancer
研究概览
简要总结
RATIONALE: Combining calcitriol with dexamethasone may increase the effectiveness of therapy by making cancer cells more sensitive to dexamethasone.
PURPOSE: Phase I trial to study the effectiveness of calcitriol combined with dexamethasone in treating patients who have prostate cancer that has not responded to previous hormone therapy.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of calcitriol administered alone and in combination with dexamethasone in patients with hormone-refractory prostate cancer.
- Determine the pharmacokinetics of calcitriol with and without dexamethasone in these patients.
OUTLINE: This is a dose-escalation study of calcitriol.
In the first stage of the study, cohorts of 3-6 patients receive escalating doses of oral calcitriol on days 1-3. Dose escalation continues until the maximum tolerated dose (MTD) is determined.
In the second stage, patients receive escalating doses of oral calcitriol on days 1-3 and a fixed dose of oral dexamethasone on days 0-4. Treatment continues weekly in the absence of disease progression or unacceptable toxicity. Dose escalation continues until the MTD is determined.
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 —（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 with progressing regional or metastatic disease despite primary hormonal therapy (bilateral orchiectomy, estrogen, or luteinizing hormone-releasing hormone (LHRH) therapy with or without simultaneous antiandrogen)
- •Documented new lesions or rising PSA (at least 50% increase on 3 measurements more than 2 weeks apart) after prior antiandrogen or progestational agent, or other hormonal agent cessation
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •WBC greater than 3,500/mm^3
- •Absolute neutrophil count greater than 1,500/mm^3
- •Platelet count greater than 100,000/mm^3
- •Bilirubin less than 2.0 mg/dL
- •SGOT less than 4 times upper limit of normal
- •Creatinine no greater than 1.8 mg/dL
- •No uncontrolled diabetes mellitus
- •Fertile patients must use effective double barrier contraception for at least 1 week before, during, and at least 2 weeks after study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Concurrent epoetin alfa for anemia allowed
- •Chemotherapy:
- •Not specified
- •Endocrine therapy:
- •See Disease Characteristics
- •At least 28 days since prior antiandrogens or progestational agents
- •Concurrent testicular androgen suppression with an LHRH analog (leuprolide or goserelin) allowed in non-orchidectomized patients
- •Radiotherapy:
- •No concurrent radiotherapy
- •Not specified
- •No concurrent bisphosphonates
排除标准
- 未提供
结局指标
主要结局
MTD of calcitriol (oral, MTW weekly + dexamethasone (oral, Sunday, Monday, Tuesday, Wednesday - SMTW) in men with hormone refractory prostate cancer
时间窗: 1 year
MTD of calcitriol (oral) administered for 3 days (Monday, Tuesday, Wednesday -MTW) weekly in men with hormone-refractory prostate cancer
时间窗: 1 year
次要结局
- pharmacokinetics of calcitriol when given as a single agent and following 3 days of dexamethasone(1 year)
- whether dexamethasone permits the administration of calcitriol without the development of hypercalcemia in patients who developed hypercalcemia while receiving calcitriol alone(1 year)
- effects of calcitriol +/- dexamethasone on serum PTH, urinary calcium and MAPK activity and VDR expression in serum, urine and PBMs , respectively, in this patient population(1 year)