临床试验/NCT00075439

NCT00075439已完成2 期

A Phase II Trial of ZD1839 (Iressa®) in Metastatic Neuroendocrine Tumors

National Cancer Institute (NCI)1 个研究点分布在 1 个国家目标入组 90 人开始时间: 2003年12月最近更新: 2013年6月4日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 90
试验地点: 1
主要终点: Proportion of patients progression-free at 6 months

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This phase II trial is studying how well gefitinib works in treating patients with progressive metastatic neuroendocrine tumors. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

详细描述

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).

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 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

排除标准

•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

研究组 & 干预措施

Arm I

Experimental

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

干预措施: gefitinib (Drug)

Arm I

Experimental

Patients receive oral gefitinib once daily 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

Proportion of patients progression-free at 6 months

时间窗: At 6 months

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.

次要结局

Incidence of adverse events graded according to NCI CTCAE version 3.0(Up to 2 years)
Confirmed tumor response to treatment will be evaluated and will be considered a PR or CR on consecutive evaluations at least 4 weeks apart(Up to 2 years)
Survival time(Time from registration to death due to any cause, assessed up to 2 years)
Time to disease progression(Time from randomization to documentation of disease progression, assessed up to 2 years)
Duration of response(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)
Time to treatment failure(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)

研究者

发起方

National Cancer Institute (NCI)

申办方类型

Nih

责任方

Sponsor

研究点 (1)

Loading locations...

相似试验

已完成

不适用

NCT00068497National Cancer Institute (NCI)40

已完成

2 期

Gefitinib in Treating Patients With Advanced Unresectable Hepatocellular Carcinoma (Liver Cancer)Adult Primary Hepatocellular CarcinomaAdvanced Adult Primary Liver CancerLocalized Unresectable Adult Primary Liver CancerRecurrent Adult Primary Liver Cancer

NCT00071994National Cancer Institute (NCI)59

已完成

2 期

Gefitinib in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung CancerBronchoalveolar Cell Lung CancerRecurrent Non-small Cell Lung CancerStage IIIB Non-small Cell Lung CancerStage IV Non-small Cell Lung Cancer

NCT00029003National Cancer Institute (NCI)90

已完成

2 期

Gefitinib in Treating Patients With Recurrent or Metastatic Esophageal or Gastroesophageal Junction CancerEsophageal Cancer

NCT00268346Case Comprehensive Cancer Center58

已完成

2 期

Gefitinib in Treating Patients With Malignant MesotheliomaAdvanced Malignant MesotheliomaEpithelial MesotheliomaRecurrent Malignant MesotheliomaSarcomatous Mesothelioma

NCT00025207National Cancer Institute (NCI)40