Phase I/II Trial Of Low Dose Suramin (CI-1003, NSC#34936) And 5-Fluorouracil In Patients With Metastatic Renal Cell Carcinoma (RCC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Dose of suramin to deliver the target plasma concentrations of 10 to 50 uM (Phase I)
研究概览
简要总结
Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Suramin may increase the effectiveness of fluorouracil by making tumor cells more sensitive to the drug. This phase I/II trial is studying the side effects and best dose of fluorouracil and the chemosensitizer suramin and to see how well they work in treating patients with metastatic renal cell (kidney) cancer.
详细描述
PRIMARY OBJECTIVES:
I. Determine the dose of suramin and fluorouracil that would result in plasma concentrations of suramin between 10-50 uM in patients with metastatic renal cell cancer. (Phase I) II. Determine the objective response rate (complete response and partial response) in patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the preliminary efficacy of this regimen in these patients. (Phase I) II. Determine the pharmacokinetics of low-dose suramin in these patients. (Phase I) III. Determine the time to tumor progression and progress rate at 3 and 6 months in patients treated with this regimen. (Phase II)
OUTLINE: This is a dose-escalation phase I study followed by a phase II 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 renal cell cancer
- •Metastatic disease
- •Measurable or evaluable disease
- •Measurable disease required for phase II
- •No untreated CNS metastasis or CNS metastases progressing ≤ 4 weeks after prior radiotherapy
- •Performance status - ECOG 0-1
- •At least 12 weeks
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 9.0 g/dL
- •AST ≤ 2.5 times upper limit of normal (ULN)
- •Alkaline phosphatase ≤ 5 times ULN
- •Bilirubin ≤ 1.5 mg/dL
- •Creatinine ≤ 1.8 mg/dL
- •Calcium ≤ ULN
- •No untreated hypercalcemia
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must be surgically sterile or use effective contraception
- •No uncontrolled diabetes mellitus
- •No known severe hypersensitivity to suramin
- •No other concurrent uncontrolled illness
- •No active or ongoing infection
- •No active autoimmune disease
- •No neuropathy ≥ grade 2
- •No psychiatric illness or social situation that would preclude study compliance
- •No other malignancy within the past 5 years except basal cell skin cancer, carcinoma in situ of the cervix, or localized prostate cancer
- •No concurrent filgrastim (G-CSF)
- •No more than 2 prior chemotherapy regimens for renal cell cancer (phase II only)
- •No concurrent corticosteroid dose more than physiologic replacement levels
- •See Disease Characteristics
- •At least 4 weeks since prior radiotherapy
- •No concurrent radiotherapy
- •Recovered from prior oncologic or other major surgery
- •At least 4 weeks since prior major surgery
- •No concurrent surgery
- •Recovered from all prior anticancer therapy other than alopecia (chronic toxicity < grade 2)
- •At least 4 weeks since prior systemic therapy
- •More than 30 days since prior investigational drugs
- •Concurrent bisphosphonates allowed
排除标准
- 未提供
研究组 & 干预措施
Treatment (suramin and fluorouracil)
PHASE I: Patients receive suramin IV over 30 minutes and fluorouracil IV on days 1, 8, 15, 22, 29, and 36. Cohorts of 3-6 patients receive escalating doses suramin and fluorouracil until the dose level allowing 10-50 uM of suramin into the patient's blood is determined without 2 or more of 6 patients experiencing dose-limiting toxicity.
PHASE II: Patients receive suramin and fluorouracil (at the dose level determined in phase I) as in phase I.
In both phases, courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Fluorouracil (Drug)
Treatment (suramin and fluorouracil)
PHASE I: Patients receive suramin IV over 30 minutes and fluorouracil IV on days 1, 8, 15, 22, 29, and 36. Cohorts of 3-6 patients receive escalating doses suramin and fluorouracil until the dose level allowing 10-50 uM of suramin into the patient's blood is determined without 2 or more of 6 patients experiencing dose-limiting toxicity.
PHASE II: Patients receive suramin and fluorouracil (at the dose level determined in phase I) as in phase I.
In both phases, courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (suramin and fluorouracil)
PHASE I: Patients receive suramin IV over 30 minutes and fluorouracil IV on days 1, 8, 15, 22, 29, and 36. Cohorts of 3-6 patients receive escalating doses suramin and fluorouracil until the dose level allowing 10-50 uM of suramin into the patient's blood is determined without 2 or more of 6 patients experiencing dose-limiting toxicity.
PHASE II: Patients receive suramin and fluorouracil (at the dose level determined in phase I) as in phase I.
In both phases, courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Suramin (Drug)
结局指标
主要结局
Dose of suramin to deliver the target plasma concentrations of 10 to 50 uM (Phase I)
时间窗: Up to 48 hours
Objective response rate (CR + PR) using RECIST criteria (Phase II)
时间窗: Up to 4 years
Summary statistics (e.g. means and standard deviations or medians and ranges, or frequency counts) and 95% confidence intervals will be calculated. Graphical models will also be used to summarize the data.
次要结局
- Progression rate (Phase II)(6 months)
- Time to disease progression (Phase II)(Up to 4 years)
- Toxicity assessed using NCI CTCAE version 3.0 (Phase II)(Up to 4 years)