CPTK787/ZK222584 IN PATIENTS WITH METASTATIC NEUROENDOCRINE TUMORS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项开放标签的II期研究，评估PTK787/ZK222584在神经内分泌肿瘤患者中每日给药的安全性和有效性，这些患者正在经历进行性疾病和/或肿瘤相关综合征症状（潮红和腹泻）被认为在最佳剂量的奥曲肽治疗下仍未得到充分控制。控制不充分定义为连续7天每天至少2次潮红或6次排便。符合所有纳入和排除标准并已完成所有基线和筛选试验的受试者将接受初始剂量PTK787/ZK222584 1,250 mg，每日一次，受试者还将继续使用每4周30 mg的山多他汀LAR计划剂量。这两种药物的剂量都是固定的毫克，而不是按体重或体表面积。PTK787/ZK222584药物将每日口服给药。PTK787/ZK222584每片250毫克。受试者将每天服用5片研究药物。受试者可以继续接受治疗，只要他们没有经历不可接受的毒性或根据实体瘤反应评估标准（RECIST）标准定义的疾病进展的证据。将对受试者进行每日日志评估，以评估症状控制程度（潮红和腹泻），每月监测受试者的生化控制情况，每三个月监测一次肿瘤反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is an open-label, phase II study evaluating the safety and efficacy of PTK787/ZK222584 administered daily in subjects with neuroendocrine tumors that are experiencing progressive disease and/or whose tumor-related syndrome symptoms (flushing and diarrhea) are considered inadequately controlled despite optimal doses of octreotide therapy. Inadequate control is defined as a minimum of 2 flushing episodes or 6 bowel movements per day for 7 consecutive days. Subjects who meet all inclusion and exclusion criteria and have completed all baseline and screening testing will receive an initial dose of PTK787/ZK222584 1,250 mg once daily and subjects will also remain on the scheduled doses of Sandostatin LAR 30 mg every 4 weeks. Both drugs will be dosed on a flat schedule of mg not by weight or body surface area. The PTK787/ZK222584 medication will be taken orally with daily dosing. Each tablet of PTK787/ZK222584 is 250 mg. The subject will take five tablets of study medication per day. Subjects may continue to receive therapy as long as they do not experience unacceptable toxicities or evidence of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Subjects will be evaluated with a daily log to assess the degree of symptom control (flushing and diarrhea) and subjects will be monitored monthly for biochemical control and every three months for tumor response.