A Phase I Study Of ZD 1839 In Combination With Radiation And Chemotherapy In Locally Advanced Squamous Cell Carcinoma Of The Head And Neck
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of grade 4 or greater skin toxicity as scored by the NCI Common Toxicity Criteria v2.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of gefitinib when given together with radiation therapy with or without cisplatin in treating patients with stage III or stage IV head and neck cancer. Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of cancer. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and radiation therapy with cisplatin may kill more tumor cells
详细描述
PRIMARY OBJECTIVES:
I. To establish the safety profile of daily oral administration of ZD1839 ("Iressa", AstraZeneca, Inc.) that can be given with concurrent irradiation alone or combined concurrently with weekly cisplatin in previously untreated patients with locally advanced HNSCC, AJCC clinical stage III-IVB, deemed not suitable for surgery. Hence, the maximum-tolerated dose of ZD1839 will be determined.
II. To delineate and quantitate any dose-dependent local and or systemic toxicities of ZD1839 given concurrently with irradiation or combined concurrently with weekly cisplatin to patients with locally advanced, HNSCC, AJCC stage III-IVB, deemed not suitable for surgery.
III. To determine the feasibility and toxicity profile of protracted continuous daily dosing of ZD1839 beginning 8 weeks after the completion of the head and neck radiation therapy for a period not to exceed 2 years.
SECONDARY OBJECTIVES:
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 locally advanced squamous cell carcinoma of the head and neck involving the oral cavity, oropharynx, hypopharynx, or supraglotticor glottic larynx
- •Unresectable disease
- •Medically inoperable resectable disease allowed
- •Stage III or IV
- •No distant metastases
- •Only patients with intermediate stage disease (T1-2, N1-N2a or T3, N0-1) are eligible for radiotherapy alone with gefitinib
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •More than 6 months
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin at least 9 g/dL
- •Bilirubin normal
- •AST and ALT no greater than 2.5 times upper limit of normal
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Medically suitable to withstand a course of definitive radiotherapy
- •No ongoing or active infection
- •No other malignancy within the past 3 years except basal cell skin cancer or carcinoma in situ of the cervix
- •No prior allergic reactions to compounds of similar chemical or biological composition to gefitinib or other study agents
- •No uncontrolled concurrent medical or psychiatric illness or social situation that would preclude study participation
- •No prior monoclonal antibodies with potential epidermal growth factor receptor (EGFR) binding therapy
- •No prior chemotherapy
- •No prior radiotherapy
- •No prior surgery except biopsy
- •No prior anti-EGFR therapy including prior tyrosine kinase inhibitors
- •No concurrent combination anti-retroviral therapy for HIV-positive patients
- •No other concurrent investigational agents
- •No other concurrent commercial or investigational agents or therapies intended to treat the malignancy
排除标准
- 未提供
研究组 & 干预措施
Treatment (gefitinib, radiation therapy, cisplatin)
See detailed description.
干预措施: gefitinib (Drug)
Treatment (gefitinib, radiation therapy, cisplatin)
See detailed description.
干预措施: radiation therapy (Radiation)
Treatment (gefitinib, radiation therapy, cisplatin)
See detailed description.
干预措施: cisplatin (Drug)
Treatment (gefitinib, radiation therapy, cisplatin)
See detailed description.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Incidence of grade 4 or greater skin toxicity as scored by the NCI Common Toxicity Criteria v2.0
时间窗: Up to 2 years
Descriptive statistics (mean, median, range, s.d., percentage, as appropriate) will be obtained.
Incidence of any other grade 4 or greater toxicity as scored by the NCI Common Toxicity Criteria v2.0
时间窗: Up to 2 years
Descriptive statistics (mean, median, range, s.d., percentage, as appropriate) will be obtained.
Incidence of grade 4 or greater mucositis as scored by the National Cancer Institute (NCI) Common Toxicity Criteria v2.0
时间窗: Up to 2 years
Descriptive statistics (mean, median, range, standard deviation \[s.d.\], percentage, as appropriate) will be obtained.
次要结局
- Primary tumor response rate as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)(8 weeks)
- Biological effects of gefitinib within the primary tumor and skin(Baseline)
- Relapse-free survival rates(Up to 5 years)
- Response rates as assessed by the RECIST(Up to 5 years)
- Overall survival rates(Up to 5 years)