A Phase II Study of Erlotinib and Radiation Therapy in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Time to Disease Progression
研究概览
简要总结
RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Erlotinib hydrochloride may also make tumor cells more sensitive to radiation therapy. Radiation therapy uses high-energy x- rays and other types of radiation to kill tumor cells. Giving erlotinib hydrochloride together with radiation therapy may be an effective treatment for patients with head and neck cancer.PURPOSE: This phase II trial is studying how well giving erlotinib hydrochloride together with radiation therapy works in treating patients with stage III-IV squamous cell cancer of the head and neck.
详细描述
PRIMARY OBJECTIVES:I. To determine the time to progression of the combination of the EGFR inhibitor erlotinib and radiation therapy. SECONDARY OBJECTIVES:I. To determine objective response rate, locoregional control rate, duration of response, patterns of failure, overall survival, toxicities and quality of life outcomes of the combination of erlotinib and concurrent radiation therapy.II. To determine the pharmacokinetic profile of erlotinib. Additional analyses of the pharmacokinetic data on patients receiving daily erlotinib treatment via their feeding tube will be conducted. III. To determine the effect of treatment and dose of treatment on biologic correlates in tumor tissue and/or surrounding mucosa, EGFR expression and phosphorylation status, serum markers of angiogenic activity VEGF, sVEGFR-2, sKIT, ICAM, PDGF, fluorescence in situ hybridization (FISH) for ERBB2 for gene amplification, DNA-sequencing of EGFR and ERBB2 genes from DNA extracted from pretreatment biopsy material for mutation screening, gene expression profiling on pre-treatment biopsy material to identify predictors of response to treatment, apoptosis (TUNEL assay), Ki67 (nuclear proliferation antigen)IV. To determine the utility of the comprehensive geriatric assessment, in predicting tolerance to treatment in patients >= 65 years included in this trial. OUTLINE: Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.After completion of study treatment, patients are followed up at 6 months, every 3 months for 2 years, and then every 6 months for 2 years.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed locally advanced (stage III or IV) squamous cell carcinoma of the head and neck without distant metastatic disease, who are not candidates or have declined definitive surgical resection or for administration of standard chemotherapy during radiation therapy because of any of the following reasons: advanced age (>= 70 years); poor ECOG performance status (2 or 3); significant comorbidities, as reflected by a Charlson comorbidity index score of >= 3; abnormal hematopoietic, hepatic or renal function; patient's decision after applicable standard treatment options have been offered and declined by patient
- •No prior chemotherapy, radiation therapy, or investigational antitumor drug
- •Measurable disease within 4 weeks prior to registration according to the recommended RECIST response criteria
- •Life expectancy of greater than 12 weeks
- •Patients must have normal hepatic function or well compensated liver disease as defined by the Child-Pugh classification of severity of liver disease; patients with hepatic impairment (total bilirubin greater than upper limit of normal [ULN] or well-compensated disease [Child-Pugh class A] enrolled in the trial will be closely monitored, especially those with total bilirubin > 3 times ULN; dosage modifications (therapy interruption or discontinuation) may be necessary for severe changes in liver function; patient management will follow the FDA-approved labeling recommendations
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation
- •Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
- •Women of childbearing potential must have a negative pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and willingness to sign a written informed consent document
排除标准
- •All histologies other than squamous cell carcinoma
- •Salivary gland paranasal sinus and nasopharyngeal squamous cell carcinoma
- •Patients who have had prior chemotherapy or radiotherapy
- •Patients with metastatic disease
- •Patients with ECOG performance status of 4
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ERLOTINIB
- •Patients with history of any other malignancy (except squamous cell or basal cell cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has elapsed since treatment of the previous cancer and the patient is currently disease-free from the previous cancer
- •Patients may not be receiving any other investigational agent
- •Pregnant women; breastfeeding should be discontinued
研究组 & 干预措施
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: intensity-modulated radiation therapy (Radiation)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacogenomic studies (Other)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: gene expression analysis (Other)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: 3-dimensional conformal radiation therapy (Radiation)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: biopsy (Other)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: questionnaire administration (Other)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: enzyme-linked immunosorbent assay (Other)
Arm I
Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: polymorphism analysis (Other)
结局指标
主要结局
Time to Disease Progression
时间窗: 1 year and 10 months following study start
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started. Disease progression free survival (PFS) is measured from start of treatment to the date of disease progression or protocol-designated outcome, whichever occurs first and censored at the date of last followed for those survivors without disease progression Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Measured via Conventional CT and MRI
次要结局
- Toxicities, Number of Persons With Adverse Events(up to 2 yrs after treatment)
- Locoregional Control Rate(5 yrs following treatment)
- Quality of Life Assessment as Measured by Functional Assessment of Cancer Therapy (FACT-G) Test(after treatment at 6 mos)
- Objective Response Rate(1 year and 10 months following study start)
- Patterns of Failure(5 yrs following treatment)