A Phase I Study Of Bevacizumab (Recombinant Humanized Monoclonal Antibody To Vascular Endothelial Growth Factor) In Addition To Flourouracil And Hydroxyurea As Initial Chemotherapy With Concomitant Radiotherapy (B-FHX) For Poor Prognosis Head And Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- MTD defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
研究概览
简要总结
Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining monoclonal antibody therapy with chemotherapy and radiation therapy may be an effective treatment for head and neck cancer. This phase I trial is to see if combining bevacizumab, fluorouracil, and hydroxyurea with radiation therapy works in treating patients who have advanced head and neck cancer
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and dose-limiting toxicity of bevacizumab when given in combination with fluorouracil, hydroxyurea, and radiotherapy in patients with advanced head and neck cancer.
II. Determine the time to progression, pattern of failure, local control, and distant failure rate in patients treated with this regimen.
III. Determine the local toxic effects of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of bevacizumab.
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 or cytologically confirmed advanced head and neck cancer
- •Requiring regional palliative radiotherapy
- •Not amenable to standard therapy
- •Previously untreated disease allowed only if prognosis is poor (i.e., estimated 2-year survival of less than 10% if treated with standard therapy alone)
- •No obvious tumor involvement of major vessels on CT scan
- •No known brain metastases
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •More than 12 weeks
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •No history of bleeding diathesis
- •Bilirubin normal
- •AST/ALT no greater than 2.5 times upper limit of normal
- •Creatinine normal
- •Urine protein no greater than trace
- •Urine protein less than 0.5 g/24 hours
- •No significant renal impairment
- •No symptomatic congestive heart failure
- •No cardiac arrhythmia
- •No deep venous thrombosis
- •No uncontrolled hypertension
- •No clinically significant peripheral artery disease
- •No arterial thromboembolic event within the past 6 months, including any of the following:
- •Transient ischemic attack
- •Cerebrovascular accident
- •Unstable angina
- •Myocardial infarction
- •No hemoptysis of at least 1 tablespoon
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in this study
- •No non-healing wounds within the past 4 weeks
- •No significant ongoing or active infection
- •No other uncontrolled illness
- •No other severe complicating medical illness that would preclude study participation
- •No psychiatric illness or social situation that would preclude study compliance
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior fluorouracil and hydroxyurea with radiotherapy
- •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •See Disease Characteristics
- •See Chemotherapy
- •At least 4 months since prior radiotherapy and recovered
- •At least 4 weeks since prior major surgery
- •No prior or concurrent chronic use of aspirin or other nonsteroidal anti-inflammatory agents
- •No other concurrent investigational agents
- •No concurrent anticoagulation therapy
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent anticancer agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive G-CSF subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: hydroxyurea (Drug)
Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive G-CSF subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: fluorouracil (Drug)
Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive G-CSF subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: bevacizumab (Biological)
Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive G-CSF subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: radiation therapy (Radiation)
Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive G-CSF subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: filgrastim (Biological)
Treatment (hydroxyurea, fluorouracil, bevacizumab, radiation)
Patients receive oral hydroxyurea every 12 hours on days 1-6, fluorouracil IV continuously on days 1-5, and bevacizumab IV over 90 minutes on day 1. Patients also undergo radiotherapy once daily on days 1-5. Patients receive G-CSF subcutaneously on days 6-12. Treatment repeats every 2 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using NCI CTCAE version 3.0
时间窗: 14 weeks
次要结局
- Objective response rate (CR+PR) assessed using RECIST criteria(Up to 9 years)
- Pattern of failure, described as locoregional, distant, or both(Up to 9 years)
- Duration of response(From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 9 years)
- Progression free survival(From the date of registration to the date of progressive disease or death, assessed up to 9 years)
- Overall survival(From the date of registration to the date of death, assessed up to 9 years)