Gefitinib in Treating Patients With Progressive Metastatic Neuroendocrine Tumors
A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors
研究概览
地位
干预/治疗
详细说明
PRIMARY OBJECTIVES:
I. To determine the 6 month progression free survival rate in patients with progressive, advanced neuroendocrine tumors treated with ZD1839.
SECONDARY OBJECTIVES:
I. Objective tumor response rate. II. Progression free survival and time to progression. III. Improvement in circulating hormone levels. IV. Overall survival V. We will explore the molecular characterization of these tumors in attempt to understand the role of EGFR expression and its inhibition with ZD1839 in neuroendocrine tumors. The measurements will be performed on pretreatment and post-treatment tumor biopsies when possible: EGFR expression and gene amplification (IHC for EGFR and phosphorylated EGFR, ISH for gene amplification); Activation of the Ras/Raf/MAPK pathway (IHC for phosphorylated MAPK); Cell proliferation (Ki-67 staining); Apoptosis (TUNEL assay).
OUTLINE: This is a multicenter study. Patients are stratified according to disease type (carcinoid vs islet cell and other neuroendocrine tumors).
Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months until disease progression and then every 6 months for up to 2 years from study entry.
研究类型
注册 (预期的)
阶段
- 阶段2
联系人和位置
学习地点
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Minnesota
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Rochester、Minnesota、美国、55905
- Mayo Clinic
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Histologically confirmed metastatic neuroendocrine neoplasms or histologic confirmation of primary neuroendocrine tumor with clear clinical evidence of metastases
- Measurable disease
Radiographic evidence of disease progression, following any prior systemic therapy, chemoembolization, embolization, or observation; for eligibility purposes, disease progression will be defined as follows:
Either of the following documented by comparison of the on-study radiographic assessment with a prior assessment of the same type performed within the previous 60 calendar weeks:
- Appearance of a new lesion
- At least 20% increase in the longest diameter (LD) of any previously documented lesion or an increase in the sum of the LDs of multiple lesions in aggregate of 20%
- ≥4 weeks from the completion of major surgery, chemotherapy or other systemic therapy and hepatic artery embolization/chemoembolization to study registration
- ≥3 weeks from the completion of radiation therapy to study registration
- Recovered sufficiently from side effects of prior therapy
- Absolute neutrophil count (ANC) ≥ 1000/mm3
- PLT ≥ 75,000/ mm3
- Hgb ≥ 8.0 g/dL
- Total bilirubin ≤ 2 x upper normal limit (UNL)
- Alkaline phosphatase ≤ 3 x UNL (5 x UNL if liver metastases present)
- AST ≤ 3 x UNL (≤ 5 x UNL if liver metastases present)
- Creatinine ≤ 1.5 x UNL
- ECOG performance score (ps) ≤ 2
- Life expectancy ≥ 24 weeks
- Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent
Exclusion Criteria:
- Thyroid carcinoma of any histology or pheochromocytoma/paraganglioma
Any of the following as this regimen may be harmful to a developing fetus or nursing child:
- Pregnant women
- Breastfeeding women
- Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
- NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown
- Anaplastic or high-grade histology
Any of the following prior therapies:
- > 1 prior systemic chemotherapy regimen (chemoembolization not counted as systemic chemotherapy)
- Prior EGFR targeted regimen (e.g. OSI-774, EKB-569, ZD1839)
- < 4 weeks from last Interferon injection
- < 2 weeks from last octreatide short acting injection or < 6 weeks long acting injection; Note: concurrent octreatide allowed if stable dose has been administered for ≥1 month, there is documented tumor progression on the current dose, and there is no current plan for increasing dose • Other concurrent treatment considered investigational
- Concurrent chemotherapy or radiation therapy
Any of the following:
- Gastrointestinal tract disease resulting in an inability to take oral medication (e.g. dysphagia or inability to swallow capsules intact).
- Requirement for IV alimentation
- Prior procedures clearly adversely affecting intestinal absorption
- Active peptic ulcer disease
- Failure to fully recover from adverse effects of prior therapies regardless of interval since last treatment
Known abnormality of cornea, such as:
- History of dry eye syndrome or Sjogren syndrome
- Congenital abnormality
- Abnormal slit-lamp examination using a vital dye (e.g.: fluorescein or Bengal-rose)
- Abnormal corneal sensitivity test (Schirmer test)
Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptoms of congestive heart failure
- Unstable angina pectoris, cardiac arrhythmia
- Psychiatric illness/social situation that would limit compliance with study requirement
- Known brain metastases; Note: These patients are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Known HIV-positive patients receiving combination anti-retroviral therapy; Note: These patients are excluded from the study because of possible pharmacokinetic interactions with ZD1839 and because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination and anti-retroviral therapy when indicated
- Concurrent or recent use (≤ 7 days prior to ZD1839 administration) of phenytoin, carbamazepine, barbiturates, rifampicin, oxcarbazepine, rifapentine, modafinil, or St. John's Wort; Note: Because these drugs induce CYP3A4 enzymes and can cause reductions in ZD1839 plasma concentrations below levels thought to be biologically active, patients with concurrent or recent use of these drugs are excluded from the study
- History of other invasive malignancy ≤ the previous 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Arm I
Patients receive oral gefitinib once daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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相关研究
口头给予
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Proportion of patients progression-free at 6 months
大体时间:At 6 months
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If patients are lost to follow-up or discontinue active monitoring prior to 6 months post-registration, we will consider censoring them for the evaluation of the primary endpoint.
Here, Kaplan-Meier methodology will be used to estimate the final success proportion (ie, 6 month success rate with a 95% confidence interval).
Otherwise, ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
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At 6 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Incidence of adverse events graded according to NCI CTCAE version 3.0
大体时间:Up to 2 years
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The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
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Up to 2 years
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Confirmed tumor response to treatment will be evaluated and will be considered a PR or CR on consecutive evaluations at least 4 weeks apart
大体时间:Up to 2 years
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The proportion of responses will be evaluated and will be tabulated.
Assuming a binomial distribution for the incidence of response, 95% confidence intervals will also be generated.
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Up to 2 years
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Survival time
大体时间:Time from registration to death due to any cause, assessed up to 2 years
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The distribution of survival time will be estimated using the method of Kaplan-Meier.
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Time from registration to death due to any cause, assessed up to 2 years
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Time to disease progression
大体时间:Time from randomization to documentation of disease progression, assessed up to 2 years
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The distribution of time to progression will be estimated using the method of Kaplan-Meier.
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Time from randomization to documentation of disease progression, assessed up to 2 years
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Duration of response
大体时间:Date from which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 2 years
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This data will be descriptively summarized and graphically evaluated.
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Date from which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 2 years
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Time to treatment failure
大体时间:Time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, refusal, or death, assessed up to 2 years
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Time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, refusal, or death, assessed up to 2 years
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合作者和调查者
调查人员
- 首席研究员:Timothy Hobday、Mayo Clinic
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- NCI-2012-02796
- N01CM62205 (美国 NIH 拨款/合同)
- MC0279
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
在美国制造并从美国出口的产品
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