A Phase I and Phase II Study of OSI-774 in Combination With Docetaxel in Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Proportion of patients with an objective response (Phase II)
研究概览
简要总结
Phase I/II trial to study the effectiveness of combining erlotinib with docetaxel in treating patients who have locally advanced, recurrent, or metastatic head and neck cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with docetaxel may kill more tumor cells.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose and dose-limiting toxicity of erlotinib when administered in combination with docetaxel in patients with locally advanced, metastatic, or recurrent squamous cell carcinoma of the head and neck.
II. Determine the response rate, duration of response, time to progression, and survival of patients treated with this regimen.
III. Determine the pharmacokinetics of this regimen in these patients. IV. Correlate the presence of PTEN, RB, P-Akt, p15, p16, cyclin D1, p27, and p53 genes in tumor tissue with response in patients treated with this regimen.
OUTLINE: This is a phase I, dose-escalation study of erlotinib followed by a phase II study.
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 squamous cell carcinoma of the head and neck meeting 1 of the following staging criteria:
- •Recurrent
- •Metastatic
- •Locally advanced and determined to be incurable by surgery or radiotherapy
- •Measurable disease
- •No known brain metastases
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •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
- •No severe pulmonary insufficiency, including chronic obstructive pulmonary disease, requiring oxygen (O2 saturation less than 90%) and/or increase in PaCO2 blood gas level greater than 50 mm Hg
- •No history of abnormality of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
- •No congenital abnormality (e.g., Fuch's dystrophy)
- •No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
- •No abnormal corneal sensitivity test (Schirmer test or similar tear production test)
- •Able to take oral medication
- •No requirement for IV alimentation
- •No active peptic ulcer disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No significant traumatic injury within the past 21 days
- •No prior allergic reactions to compounds of similar chemical or biological composition to study drugs
- •No grade 2 or greater persistent peripheral neuropathy
- •No other concurrent uncontrolled illness that would preclude study participation
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No prior immunotherapy for head and neck cancer
- •No more than 1 prior chemotherapy regimen in the adjuvant or neoadjuvant setting
- •No more than 1 prior chemotherapy regimen for metastatic disease
- •No prior docetaxel (phase II only)
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No prior hormonal therapy for head and neck cancer
- •Prior external beam radiotherapy allowed
- •At least 4 weeks since prior radiotherapy and recovered
- •More than 21 days since prior major surgery
- •No prior surgery affecting gastrointestinal absorption
- •No prior epidermal growth factor receptor-targeting therapy
- •No other concurrent investigational agents
- •No other concurrent anticancer therapies or agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
排除标准
- 未提供
研究组 & 干预措施
Arm I
PHASE I: Patients receive oral erlotinib once daily on days 1-28 and docetaxel IV over 1 hour on days 8, 15, and 22. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6 patients receives erlotinib at the MTD.
PHASE II: Patients receive erlotinib at the MTD and docetaxel as in phase I.
干预措施: erlotinib hydrochloride (Drug)
Arm I
PHASE I: Patients receive oral erlotinib once daily on days 1-28 and docetaxel IV over 1 hour on days 8, 15, and 22. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6 patients receives erlotinib at the MTD.
PHASE II: Patients receive erlotinib at the MTD and docetaxel as in phase I.
干预措施: docetaxel (Drug)
Arm I
PHASE I: Patients receive oral erlotinib once daily on days 1-28 and docetaxel IV over 1 hour on days 8, 15, and 22. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6 patients receives erlotinib at the MTD.
PHASE II: Patients receive erlotinib at the MTD and docetaxel as in phase I.
干预措施: laboratory biomarker analysis (Other)
Arm I
PHASE I: Patients receive oral erlotinib once daily on days 1-28 and docetaxel IV over 1 hour on days 8, 15, and 22. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6 patients receives erlotinib at the MTD.
PHASE II: Patients receive erlotinib at the MTD and docetaxel as in phase I.
干预措施: pharmacological study (Other)
结局指标
主要结局
Proportion of patients with an objective response (Phase II)
时间窗: Up to 6 years
Maximum tolerated dose of erlotinib and docetaxel, based on incidence of DLT graded according to NCI CTC version 2.0 (Phase I)
时间窗: Up to 28 days
次要结局
- Median survival (Phase II)(Up to 6 years)
- Time to tumor progression (Phase II)(Up to 6 years)
- Response rate as measured by RECIST criteria (Phase II)(Up to 6 years)