Phase Ib Study of Erlotinib Prior to Surgery in Patients With Head and Neck Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Change in modulation of the biomarker phospho-Akt in tumor specimens
研究概览
简要总结
This randomized phase Ib trial studies standard-dose or high-dose erlotinib hydrochloride before surgery in treating patients with head and neck cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the effects of erlotinib (erlotinib hydrochloride) 150 mg/day (standard dose) and 200 mg/day or 300 mg/day (high-dose) on the phosphorylation of AKT protein downstream from epidermal growth factor receptor (EGFR).
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of erlotinib 150 mg/day (standard dose) and 200 mg/day or 300 mg/day (high-dose).
II. To correlate the effects of erlotinib on the phosphorylation of AKT with the immunohistochemical expression level of EGFR and the level of amplification of the EGFR gene as determined by fluorescent in situ hybridization (FISH).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Patients with histologically confirmed cancer of the head and neck. Patients with salivary gland tumors and squamous cell carcinomas of the skin are also eligible. (Note: Any patient with a diagnosis of aggressive squamous cell carcinoma of the skin and determined to be surgically resectable will be considered for eligibility. These patients are typically seen in the Head & Neck surgery clinic and decisions for study consideration will be based on consultations with the department of Head & Neck surgery.)
- •The patient must have biopsy-accessible disease.
- •Patients must be surgical candidates (either definitive or palliative setting).
- •Patients may have received prior therapy including cytotoxic chemotherapy (e.g. platinum drugs and taxanes) and radiation therapy.
- •Patients must have a performance score (ECOG) of 0-
- •Patients should have adequate bone marrow function, as defined by peripheral granulocyte count of >/= 1,000/mm³, and a platelet count of >/= 50,000/mm³.Patients must have adequate liver function with a bilirubin </= 1.5 times the upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be </= 2 x the ULN and alkaline phosphatase must be </= 2 x ULN.
- •Patients should have adequate renal function (serum creatinine </= 1.5 x ULN).
- •Age >/= 18 years
- •Ability to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of the study, in keeping with institutional policy
- •Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months,who have not had tubal ligation or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study,she should inform her treating physician immediately.The patient,if a man,agrees to use effective contraception or abstinence.
排除标准
- •Patients with prior exposure to small molecule tyrosine kinase inhibitors or EGFR-targeted antibodies within the past 6 months.
- •Patients for whom, in the opinion of the treating surgeon, the administration of erlotinib would cause a deleterious delay in surgical treatment.
- •Patients with uncompensated congestive cardiac failure.
- •Patients with an organ allograft.
- •Patients with a serious concurrent infection or illness including, but not limited to, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that could limit compliance with study requirements.
- •Female patients who are pregnant or breastfeeding
- •Patients currently on chemotherapy, immunotherapy, or therapy with monoclonal antibodies or other investigational agents with anti-tumor activity
研究组 & 干预措施
Arm I (standard-dose erlotinib hydrochloride)
Patients receive standard-dose erlotinib hydrochloride PO QD for 2-3 weeks (up to 8 weeks if surgery is delayed).
干预措施: Erlotinib Hydrochloride (Drug)
Arm I (standard-dose erlotinib hydrochloride)
Patients receive standard-dose erlotinib hydrochloride PO QD for 2-3 weeks (up to 8 weeks if surgery is delayed).
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (high-dose erlotinib hydrochloride)
Patients receive high-dose erlotinib hydrochloride PO QD for 2-3 weeks (2-8 weeks for current smokers or up to 8 weeks if surgery is delayed).
干预措施: Erlotinib Hydrochloride (Drug)
Arm II (high-dose erlotinib hydrochloride)
Patients receive high-dose erlotinib hydrochloride PO QD for 2-3 weeks (2-8 weeks for current smokers or up to 8 weeks if surgery is delayed).
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Change in modulation of the biomarker phospho-Akt in tumor specimens
时间窗: From baseline to surgery
Modulation of phospho-Akt (difference in immunohistochemistry \[IHC\] score between the surgical specimen and the baseline biopsy) will be compared between the two treatment arms (i.e., standard-dose and high-dose) with the use of Wilcoxon rank sum test.
次要结局
未报告次要终点