NCT00063895已完成1 期
A Pharmacogenetic and Pharmacodynamic Study of Erlotinib (OSI-774) Toxicity in Patients With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
研究概览
简要总结
This phase I/II trial is studying the side effects of erlotinib and to see how well it works in treating patients with metastatic or unresectable non-small cell lung cancer, ovarian cancer, or squamous cell carcinoma (cancer) of the head and neck. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth
详细描述
PRIMARY OBJECTIVES:
I. To determine if a significant correlation exists between the length of the CA dinucleotide repeat polymorphism in the EGFR gene and observed toxicity in patients treated with OSI-774.
SECONDARY OBJECTIVES:
I. To study the pharmacodynamic effects of OSI-774 on EGFR activity and MAP kinase signaling using skin as a surrogate tissue.
II. To determine if interindividual variation of OSI-774 pharmacokinetics is related to a previously described CYP3A5 genetic polymorphism.
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
- •Patients must have histologically or cytologically confirmed metastatic or unresectable non-small cell lung cancer, squamous cell carcinoma of the head and neck, or ovarian cancer
- •Eligible patients must have been off previous anticancer therapy including chemotherapy, radiotherapy, biological therapy, or other investigational therapy for at least 4 weeks before study entry (6 weeks if prior therapy included nitrosoureas or mitomycin C)
- •ECOG performance status =< 2 (Karnofsky >= 60%)
- •Life expectancy of greater than 12 weeks
- •Leukocytes >= 3,000/ul
- •Absolute neutrophil count >= 1,500/ul
- •Platelets >= 100,000/ul
- •Total bilirubin within normal institutional limits
- •Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Patients must have measurable or assessable disease
- •The effects of OSI-774 on the developing human fetus are unknown; for this reason women of childbearing potential and men 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; 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 the willingness to sign a written informed consent document
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients with prior treatment with small molecule inhibitors of EGFR, including erlotinib and gefitinib, are not eligible for this study
- •Patients may not be receiving any other investigational agents
- •Patients with uncontrolled brain metastasis; patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 4 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study because OSI-774 is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OSI-774, breastfeeding should be discontinued if the mother is treated with either agent
- •HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- •Patients with significant ophthalmologic abnormalities, including: severe dry eye syndrome, kerato-conjunctivitis sicca, Sjogren's syndrome, severe exposure keratopathy, disorders that might increase the risk for epithelium-related complications (e.g. bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis); patients with mild forms of any of the above, an asymptomatic history, or a normal ophthalmologic examination may be considered for inclusion at the discretion of the investigator; an ophthalmologic exam is not needed prior to this study unless clinically indicated; patients with treatable conditions (e.g. infectious keratitis/conjunctivitis, allergic conjunctivitis) may be reevaluated for study eligibility after treatment or resolution of the condition; use of contact lenses during the course of this trial may increase the risk of corneal complications and will be strongly discouraged
- •Serious, non-healing wound ulcer, or bone fracture
- •Major surgical procedure, open biopsy or significant traumatic injury within 14 days prior to Day 1; following such procedures or injuries, wound healing should be evident prior to initiation of therapy
研究组 & 干预措施
Treatment (erlotinib hydrochloride)
Experimental
Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Treatment (erlotinib hydrochloride)
Experimental
Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (erlotinib hydrochloride)
Experimental
Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacogenomic studies (Other)
Treatment (erlotinib hydrochloride)
Experimental
Patients receive oral erlotinib on days 1-28. Courses repeat every 28 days 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
Rate of diarrhea and skin rash across the short, medium, and long genotype frequencies of the CA polymorphism
时间窗: Week 6
Compared using Armitage's test for a trend in proportions. In the event that the relationship between toxicity and length of the polymorphism is not monotone, a two degree-of-freedom chisquare test will be used in place of the trend test. The number of CA repeats treated as a continuous variable by averaging the number of repeats on each chromosome. Logistic regression analysis will then be performed to model the probability of toxicity as a function of the average length.
次要结局
- All observed toxicities(Up to 4 years)
- Pharmacodynamic effects of erlotinib hydrochloride on EGFR activity and MAP kinase signaling(Week 1)
- Observed anti-tumor responses(Up to 4 years)
- Erlotinib hydrochloride AUC(Baseline, 0.5, 1, 2, 4, and 6 h after initiation, and pre-treatment days 15 and 29)
研究者
研究点 (1)
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