COG ADVL0214: A PHASE I STUDY OF SINGLE AGENT OSI-774 (TARCEVA)

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。这项研究最近已接近尾声。正式关闭通知随本状态报告一起提交，日期为2006年1月20日。我们希望将这项研究转移到“COG ltf1 -先前进入儿童癌症组临床试验的患者的长期随访- irb # 97-0131-09”，以维持未来的随访数据提交和检索，因为本研究的分析尚未完成。我们没有在这个地点积极登记的病人。下面是这项研究的摘要，供您参考。这项第一阶段的研究测试了一种名为OSI-774的新型实验性药物的安全性，该药物可以单独使用，也可以与替莫唑胺（temozolomide）联合使用。替莫唑胺是一种抗肿瘤药物，已经被用于治疗其他类型的癌症。用OSI-774对癌细胞进行的实验室实验表明，OSI-774通过影响细胞执行许多正常功能的能力来减缓细胞生长。已在成人人群中测试了osii -774以及osii -774与替莫唑胺的组合，替莫唑胺已在儿童中使用。OSI-774尚未在儿童中进行测试。这项研究的目的是测试osii -774本身以及与替莫唑胺一起用于儿童的安全性，看看它们对儿童和儿童癌症有什么影响（好的和坏的），并找出在不造成严重副作用的情况下可以给儿童服用的osii -774的最高剂量。这项研究的其他目标是了解人体如何处理这种药物，并了解OSI-774对肿瘤组织的影响。这项研究是这样设计的，孩子们被分成3或6个小组。第一组儿童将以起始剂量给予osii -774，并将监测是否有严重副作用。如果第一组儿童的副作用不是太严重，那么下一组儿童将被给予更高剂量的osii -774，下一组则给予更高剂量。这个过程将继续进行，直到发现最大剂量不会导致不可接受的副作用。osi774和替莫唑胺的剂量不会对每个儿童增加，但如果发现严重的副作用可能会减少。每个疗程持续28天。在第一个疗程中只服用OSI-774。OSI-774以液体形式存在，可以注入静脉；然而，在这项研究中，OSI-774液体与一种甜味调味溶液混合，供儿童饮用。在药物治疗的第二个疗程和之后的每个疗程中，孩子将继续每天喝一次osi774液体和替莫唑胺，在每个疗程的前五天服用药片。替莫唑胺药片可以打开并混合在苹果酱或苹果汁中。治疗过程概述如下：第1天1-28天OSI-774 (OSI) OSI第2天及以上第1天2 3 4 5 6-28天OSI-774 (OSI) OSI OSI OSI OSI OSI OSI OSI OSI替莫唑胺（TEM） TEM TEM TEM TEM TEM TEM TEM TEM

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 study has recently closed to accrual. The official notice of closure is submitted with this status report and is dated 01/20/2006. We would like to transfer this study to "COG LTF1-Long Term Follow up of Patients Previously Entered on Children's Cancer Group Clinical Trials-IRB # 97-0131-09" to maintain future follow up data submission and retrieval, as analysis is not yet completed for this study. We have no patients actively enrolled at this site. An abstract of the research is provided below for your review. This phase I study tests the safety of a new experimental drug called OSI-774, alone and in combination with temozolomide, which is an anti-tumor drug already being used to treat other types of cancer. Laboratory experiments performed with OSI-774 on cancer cells showed that OSI-774 works to slow cell growth by affecting the ability of the cell to carry out many normal functions. OSI-774 and the combination of OSI-774 and temozolomide have been tested in the adult population, and temozolomide has been used in children. OSI-774 has not been tested in children. The goals of this study are to test the safety of OSI-774, by itself and also with temozolomide in children, to see what effects (good and bad) they have on children and children's cancer, and to find the highest dose of OSI-774 that can be given to children without causing serious side effects. Other goals of this study are to learn how the body handles the drug, and to understand the effects OSI-774 has on tumor tissue. The study is designed such that the children are separated into groups of 3 or 6. The first group of children will be given OSI-774 at the starting dose and will be monitored for serious side effects. If the side effects are not too serious for the first group of children, the next group of children will be given a higher dose of OSI-774, and the next group a higher dose. This process will continue until the maximum dose is found that does not result in unacceptable side effects. The doses of OSI-774 and temozolomide given will not be increased for each individual child, but may be decreased if serious side effects are seen. Each course of therapy will last 28 days. Only the OSI-774 will be taken during the first course of therapy. OSI-774 comes in a liquid form that can be given into a vein; however, in this study the OSI-774 liquid is mixed with a sweet-tasting flavoring solution for the child to drink. During the second course of drug therapy and during each course after that, the child will continue to drink the OSI-774 liquid once each day along with temozolomide, taken as pills for the first five days of each course. The temozolomide pills can be opened up and mixed in applesauce or apple juice. An outline of the treatment course is outlined below: Course 1 Days 1-28 OSI-774 (OSI) OSI Courses 2 and higher Days 1 2 3 4 5 6-28 OSI-774 (OSI) OSI OSI OSI OSI OSI OSI Temozolomide (TEM) TEM TEM TEM TEM TEM