A Dose Finding Phase I Trial of the Combination of Topotecan and PS-341, a Novel Proteasome Inhibitor, in Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Dose limiting toxicities
研究概览
简要总结
Drugs used in chemotherapy such as topotecan use different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining topotecan with bortezomib may kill more tumor cells. This phase I trial is studying the side effects and best dose of topotecan and bortezomib when given together in treating patients with metastatic or unresectable cancer
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety of the combination of PS-341 and topotecan. II. Determine the dose limiting toxicities and maximum tolerated dose as well as the recommended phase II doses of the combination.
III. Assess the pharmacokinetics of topotecan alone and in combination with PS-341.
SECONDARY OBJECTIVES:
I. Estimate the objective response rate of a combination of PS-341 and topotecan delivered on days 1-5 every three weeks as defined by the RECIST criteria.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- •Tumor accessible to core needle biopsy and willingness to undergo this procedure prior to the start of treatment
- •Evaluable disease as defined in the RECIST criteria
- •ECOG performance status =< 2
- •Life expectancy of greater than 3 months
- •Absolute neutrophil count > 1,500/ul
- •Platelets > 100,000/ul
- •Total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
- •Creatinine < 2.0 mg/ml
- •Ability to understand and the willingness to sign a written informed consent document
- •Metastatic brain or meningeal tumors are allowed if the patient is > 1 month from surgery and/or radiation and is clinically stable with respect to the tumor at the time of the study entry and currently off corticosteroids
- •Pregnancy test for pre-menopausal women
- •The effects of PS-341 and topotecan on the developing human fetus are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
排除标准
- •Creatinine clearance < 40 mL/min
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- •Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients may not be receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, PS-341 or other agents used in this study
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because topotecan is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with topotecan and PS-341, breastfeeding should be discontinued; these potential risks may also apply to other agents used in this study
- •Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with topotecan and PS-341 or other agents administered during the study.; appropriate studies will be undertaken for patients receiving combination anti-retroviral therapy when indicated
研究组 & 干预措施
Treatment (topotecan hydrochloride, bortezomib)
Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: topotecan hydrochloride (Drug)
Treatment (topotecan hydrochloride, bortezomib)
Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Treatment (topotecan hydrochloride, bortezomib)
Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (topotecan hydrochloride, bortezomib)
Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Dose limiting toxicities
时间窗: Up to 3 years
Maximum tolerated dose (MTD)
时间窗: 21 days
次要结局
- Pharmacokinetics of topotecan hydrochloride(5 minutes immediately after sample collection)
- Levels of topoisomerase I(Up to 3 years)
- DNA repair enzymes(Up to 3 years)
- Objective response according to the RECIST criteria(Up to 3 years)