A Phase I, and Biologic Correlative Study of Erlotinib, in Combination With Cetuximab and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of erlotinib hydrochloride combined with cetuximab determined by dose-limiting toxicities (DLT) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 (Part I)
研究概览
简要总结
This randomized phase I/II trial studies the side effects, best way to give, and best dose of erlotinib and bevacizumab when given with cetuximab and how well giving erlotinib and cetuximab together with or without bevacizumab works in treating patients with metastatic or unresectable kidney, colorectal, head and neck, pancreatic, or non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with cetuximab and/or bevacizumab may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of erlotinib when combined with cetuximab in patients with metastatic or unresectable renal cell, colorectal, head and neck, pancreatic, or non-small cell lung cancer (part 1).
II. Determine the MTD of bevacizumab when combined with cetuximab and erlotinib in these patients (part 2).
III. Determine the toxic effects, both quantitatively and qualitatively, of these regimens in these patients.
IV. Determine the antitumor activity of these regimens, in terms of tumor response, short-term survival, and progression-free survival, in these patients.
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
- •One of the following histologically confirmed diagnoses:
- •Renal cell cancer
- •Clear cell histology
- •Metastatic or unresectable disease AND meets 1 of the following criteria:
- •Recurrent disease
- •Refractory to interleukin-2 (IL-2)- or interferon-based therapy
- •Previously untreated AND not a candidate for IL-2-based therapy
- •Colorectal, head and neck, pancreatic, or non-small cell lung cancer
- •Metastatic or unresectable disease
- •Progression after prior standard treatment
- •No evidence of CNS disease, including the following (part 2 only):
- •Primary brain tumor
- •Brain metastases
- •Paraffin embedded tumor blocks available
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •More than 12 weeks
- •Absolute neutrophil count ≥ 1,500 mm^3
- •Platelet count ≥ 100,000 mm^3
- •Bilirubin ≤ 1.5 mg/dL
- •AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastasis is present)
- •PTT and INR ≤ 1.5, unless receiving full-dose warfarin (part 2 only)
- •Creatinine ≤ 1.5 times ULN
- •Creatinine clearance ≥ 60 mL/min
- •Calcium < 10 mg/dL (hypocalcemic agents allowed)
- •No proteinuria*
- •Protein < 1 g on 24-hour urine collection*
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No symptomatic congestive heart failure
- •None of the following are allowed for part 2:
- •Myocardial infarction within the past 6 months
- •New York Heart Association class II-IV heart disease
- •Serious cardiac arrhythmia requiring medication
- •Peripheral vascular disease ≥ grade II
- •Recent history of cerebrovascular accident
- •Uncontrolled hypertension (blood pressure ≥ 150/85 mm Hg despite medication)
- •Other clinically significant cardiovascular disease
- •No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
- •No GI tract disease resulting in a requirement for IV alimentation
- •No active peptic ulcer disease
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
- •No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (part 2 only)
- •No ongoing or active infection
- •No active infection requiring parenteral antibiotics (part 2 only)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 2 months after study treatment
- •No significant traumatic injury within the past 28 days (part 2 only)
- •No history of abnormalities of the cornea (e.g., dry eye syndrome, Sjögren's syndrome, or congenital abnormality [e.g., Fuch's dystrophy])
- 另有 26 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)
Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.
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.
Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.
Cohorts of 3-6 patients receive escalating doses of bevacizumab until the 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.
In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: erlotinib hydrochloride (Drug)
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)
Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.
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.
Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.
Cohorts of 3-6 patients receive escalating doses of bevacizumab until the 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.
In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: cetuximab (Biological)
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)
Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.
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.
Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.
Cohorts of 3-6 patients receive escalating doses of bevacizumab until the 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.
In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: bevacizumab (Biological)
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)
Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22.
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.
Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15.
Cohorts of 3-6 patients receive escalating doses of bevacizumab until the 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.
In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum tolerated dose (MTD) of erlotinib hydrochloride combined with cetuximab determined by dose-limiting toxicities (DLT) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 (Part I)
时间窗: 28 days
The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
MTD of bevacizumab combined with cetuximab and erlotinib hydrochloride determined by DLT graded according to the CTCAE version 3 (Part II)
时间窗: 28 days
The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
次要结局
- Antitumor activity defined as the number and extent (complete or partial) objective responses as well as objective stable disease as measured by RECIST criteria(6 months)
- Median time to progression(Up to 1 month)
- Progression-free survival(From the start of the treatment until the date the criteria for progression are met or the date the patient is taken off study for any reason, assessed up to 1 month)