Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 14
- 主要终点
- Maximum tolerated dose (MTD) of fenretinide
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of fenretinide in treating patients with metastatic or unresectable malignant solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of fenretinide in patients with metastatic or unresectable malignant solid tumors.
- Determine the toxic effects of this drug in these patients.
- Determine the pharmacokinetics and in vivo activity of this drug in these patients.
- Determine, preliminarily, disease or tumor response in patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive fenretinide IV continuously on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete or partial response may continue to receive fenretinide at the discretion of the study chair.
Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
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
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed solid tumor malignancy
- •Metastatic and/or unresectable disease
- •No standard curative or palliative measures exist or remain effective
- •Measurable or evaluable disease
- •No known brain metastases unless previously resected or irradiated with no treatment with steroids for more than 1 month
- •PATIENT CHARACTERISTICS:
- •ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
- •Life expectancy > 3 months
- •WBC ≥ 3,000/mm³
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 75,000/mm³
- •Bilirubin < 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN (5 times ULN for patients with known liver metastases)
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception prior to, during, and for ≥ 6 months after completion of study treatment
- •No uncontrolled diabetes mellitus at high risk for hypertriglyceridemia (i.e., fasting serum glucose concentration > 200 mg/dL OR hemoglobin A1C > 7.5%)
- •No egg allergy
- •No history of allergic reactions to compounds of similar chemical or biologic composition to fenretinide (e.g., isotretinoin, vitamin A, or tretinoin)
- •No uncontrolled intercurrent illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situation that would preclude compliance with study requirements
- •No known hypertriglyceridemia requiring medication
- •No identified familial hyperlipidemia disorder
- •PRIOR CONCURRENT THERAPY:
- •Recovered from all prior therapy
- •Prior treatment with oral fenretinide is allowed provided no severe toxicity occurred
- •At least 2 weeks since prior major surgery
- •More than 4 weeks since prior chemotherapy or radiotherapy
- •At least 6 weeks since prior nitrosoureas or mitomycin C
- •No other concurrent investigational agents
- •No other concurrent anticancer chemotherapy
- •No other concurrent antioxidants*
- •No concurrent hormone-ablative agents, including steroids, except for adrenal replacement or anti-inflammatory indications
- •No other concurrent anticancer agents or therapies
- •No concurrent herbal or other alternative therapies*
- •No concurrent vitamin supplements (e.g., vitamin A, ascorbic acid, or vitamin E)*
- •Standard-dose multivitamin allowed
- •No other concurrent medications that may act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, p-glycoprotein, multidrug resistance protein 1 (MRP1), or MRP1 drug/lipid transporters, including any of the following*:
- •Cyclosporine or any of its analogues
- •Verapamil
- •Tamoxifen or its analogue
- •Ketoconazole
- •Chlorpromazine
- •Mifepristone
- 另有 11 项未显示
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated dose (MTD) of fenretinide
时间窗: at end of study
Toxicity as measured by type (organ affected or laboratory determination such as absolute neutrophil count), severity (NCI CTCAE v3.0), time of onset (course number), duration, and reversibility or outcome
时间窗: ongoing
Survival and time to failure as measured by Kaplan-Meier
时间窗: at end of study
次要结局
未报告次要终点