Phase I/II Trial of ZD1839 and Celecoxib in Ex-Smokers

ZD1839 和塞来昔布在戒烟者中的 I/II 期试验

• 批准号: 6952320
• 负责人: MICHAEL J KELLEY
• 金额: $ 47.75万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-26 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6952320
• 关键词: antineoplastics; biomarker; chemoprevention; clinical research; clinical trial phase I; combination chemotherapy; cooperative study; dosage; drug screening /evaluation; epidermal growth factor; growth factor receptors; human subject; human therapy evaluation; kinase inhibitor; lung neoplasms; oxidoreductase inhibitor; patient oriented research; pharmacokinetics; prostaglandin endoperoxide synthase; respiratory disorder chemotherapy; respiratory epithelium; respiratory pharmacology

DESCRIPTION (provided by applicant): Cigarette smoking is causally associated with development of cancer of the lung, head & neck region, esophagus, bladder, and other sites by overwhelming epidemiological and biologic evidence. Cessation of smoking results in a slow decline in risk of cancer development that remains elevated compared to never smokers beyond 15 years after smoking cessation. Thus, strategies to reduce the impact of lung cancer in former smokers are needed. The epidermal growth factor receptor (EGFR) and cyclo-oxygenase II (COX-2) have been implicated in the development and maintenance of lung cancer. Clinical trials of the EGFR tyrosine kinase inhibitor, ZD1839, in patients with established cancer have demonstrated biological and anti-tumor effects. In the first part of this application, a Phase I, open-label, dose escalation clinical trial will be conducted to determine the maximal tolerable dose of ZD1839, and the associated effect on EGFR signaling, when used as a chemopreventive agent in former smokers. Former smokers treated with curative intent for early stage lung or head and neck cancer will be treated in cohorts of escalating doses of ZD1839. Measures of drug effect (EGFR, c-fos, apoptosis) and biomarkers of lung cancer risk will be measured in bronchial epithelium before and after taking drug for 12 weeks. Potential efficacy of EGFR and/or COX-2 inhibition (using ZD1839 and Celecoxib, respectively) will then be assessed in a Phase II, placebo-controlled, clinical trial assessing effect on bronchial epithelial genetic loss and other surrogate biomarkers of lung cancer risk.

描述（由申请人提供）：吸烟是因果关系 随着肺癌，头颈癌的发展，食道， 膀胱和其他地点通过压倒性的流行病学和生物学 证据。停止吸烟会导致癌症风险的缓慢下降 与从未吸烟超过15年相比，保持升高的开发 戒烟后。因此，减少肺癌影响的策略 在以前的吸烟者中。表皮生长因子受体（EGFR）和 环氧酶II（COX-2）与发育有关 维持肺癌。 EGFR酪氨酸激酶的临床试验 抑制剂，ZD1839，已证明已建立癌症患者 生物学和抗肿瘤作用。在本应用程序的第一部分中 第一阶段，开放标签，剂量升级临床试验将进行 确定ZD1839的最大耐受剂量，并对相关的影响 EGFR信号传导，用作前吸烟者的化学预防剂。以前的 吸烟者用治疗早期肺或头颈治疗的治疗意图 癌症将在ZD1839升级剂量的同类中进行治疗。措施 药物作用（EGFR，C-FOS，凋亡）和肺癌风险的生物标志物将 在服用药物12周之前和之后，在支气管上皮中进行测量。 EGFR和/或COX-2抑制的潜在功效（使用ZD1839和 然后，将分别在II期中评估Celecoxib，安慰剂对照， 临床试验评估对支气管上皮遗传的影响 肺癌风险的损失和其他替代生物标志物。