A Phase Ib Multicenter Trial To Determine The Safety, Tolerance And Preliminary Antineoplastic Activity Of Gemcitabine Administered In Combination With Escalating Oral Doses Of OSI-774 To Patient Cohorts With Recently Diagnosed, Gemcitabine-Naive, Advanced Pancreatic Carcinoma Or Other Potentially Responsive Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 试验地点
- 4
研究概览
简要总结
RATIONALE: Erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with gemcitabine may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of combining erlotinib with gemcitabine in treating patients who have newly diagnosed locally advanced or metastatic pancreatic cancer or other solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of erlotinib in combination with gemcitabine in patients with recently diagnosed, gemcitabine-naive, locally advanced or metastatic pancreatic carcinoma or other potentially responsive solid tumor.
- Determine the safety and tolerability of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the objective antitumor response rate and response duration in patients treated with this regimen.
- Determine the time to disease progression and duration of overall survival in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of erlotinib.
Patients receive gemcitabine IV over 30 minutes on day 1 of weeks 1-7 and oral erlotinib once daily beginning on day 3 of week 1 and continuing for 8 weeks (course 1). Patients receive subsequent courses of therapy comprising gemcitabine once weekly for 3 weeks and erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are accrued and treated at the MTD as above.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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 locally advanced or metastatic epithelial carcinoma of the pancreas or other malignancy considered to be potentially responsive to gemcitabine
- •Newly diagnosed or gemcitabine naive
- •Measurable or evaluable disease
- •Not amenable to surgical intervention due to medical contraindications or non-resectability of the tumor
- •No islet cell tumors or other non-epithelial cell carcinomas of the pancreas
- •No active CNS metastases or leptomeningeal disease
- •Treated or asymptomatic brain metastases are allowed if on a stable dose of corticosteroids and/or there is no change in brain disease status for at least 4 weeks after related therapy (e.g., whole-brain radiotherapy)
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 70-100%
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 2.0 mg/dL (except for documented Gilbert's syndrome)
- •AST or ALT less than 2 times upper limit of normal (ULN) (no greater than 5 times ULN if hepatic obstruction or metastases present)
- •Albumin at least 2.5 g/dL
- •Creatinine less than 1.5 times ULN OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular:
- •No significant cardiovascular disease
- •No history of congestive heart failure currently requiring therapy
- •No ventricular arrhythmia requiring anti-arrhythmic therapy
- •No severe conduction disturbances
- •No angina pectoris requiring therapy
- •No myocardial infarction within the past 6 months
- •Gastrointestinal:
- •No significant gastrointestinal abnormalities including:
- •Requirement for IV alimentation
- •Active peptic ulcer disease
- •Ophthalmic:
- •No significant ophthalmologic abnormalities including:
- •Severe dry eye syndrome
- •Keratoconjunctivitis sicca
- •Sjogren's syndrome
- •Severe exposure keratopathy
- •Disorders that would increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
- •Abnormal Schirmer test (less than 2 mm) allowed provided there is no evidence of clinically significant corneal surface abnormalities
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No known or suspected hypersensitivity to gemcitabine
- •No uncontrolled infection
- •HIV negative
- •No other malignancy within the past 5 years except treated non-melanoma skin cancer or carcinoma in situ of the breast or cervix
- •No other life-threatening illness
- •No psychiatric disorders or altered mental status the would preclude informed consent or study
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排除标准
- 未提供