A Phase I and Pharmacokinetic Study of Oxaliplatin (Eloxatin™) in Combination With Bortezomib (PS-341, Velcade™) in Patients With Advanced Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Probability of dose escalation according to true dose limiting toxicity (DLT) rate, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
研究概览
简要总结
Phase I trial to study the effect on the body of combining oxaliplatin with bortezomib in treating patients who have metastatic or unresectable cancer. Drugs used in chemotherapy such as oxaliplatin use different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for tumor cell growth. Combining oxaliplatin with bortezomib may kill more cancer cells
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of oxaliplatin and bortezomib in patients with advanced malignancy.
II. Determine the dose-limiting toxicity of this regimen in these patients. III. Determine the toxicity profile of this regimen in these patients. IV. Determine the antitumor activity of this regimen in these patients. V. Determine the pattern of neurotoxicity and its reversibility in patients responding to prolonged administration of this treatment regimen.
VI. Determine whether the pharmacokinetics and pharmacodynamics of oxaliplatin or bortezomib are altered by the administration of the other agent in these patients.
OUTLINE: This is a dose-escalation study.
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
- •Histologically confirmed malignancy for which standard curative or palliative measures do not exist or are no longer effective
- •Metastatic or unresectable disease
- •No known brain metastases
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100
- •More than 6 months
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •AST and ALT no greater than 5 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to any platinum or other study agents
- •No pre-existing peripheral neuropathy
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No other concurrent uncontrolled illness
- •Prior thalidomide allowed provided patient has no clinical neuropathy
- •Prior platinum or antitubulin agents allowed provided patient has no clinical neuropathy
- •At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
- •More than 3 weeks since prior radiotherapy and recovered
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent investigational or commercial agents or therapies for the malignancy
排除标准
- 未提供
研究组 & 干预措施
Treatment (oxaliplatin, bortezomib)
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the MTDs are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: oxaliplatin (Drug)
Treatment (oxaliplatin, bortezomib)
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the MTDs are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: bortezomib (Drug)
Treatment (oxaliplatin, bortezomib)
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the MTDs are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (oxaliplatin, bortezomib)
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and bortezomib IV over 3-5 seconds on days 1, 4, 15, and 18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and bortezomib until the MTDs are determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Probability of dose escalation according to true dose limiting toxicity (DLT) rate, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
时间窗: Up to 28 days
次要结局
- Area under the curve (AUC) estimates(Days 1 and 15 (course 1))
- Pharmacodynamic assessments (20S proteasome inhibition data)(Days 1 and 15 (course 1))
- Sequence of drug administration in terms of PK interaction(Days 1 and 15 (course 1))