A PHASE I TRIAL OF INTRAPERITONEALLY ADMINISTERED Y-90 CHIMERIC T8466 ANTI-CEA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。患有晚期癌症的受试者将被要求参与这项研究，该受试者会产生一种名为CEA(癌胚抗原)的无毒物质，这种物质主要局限于腹膜腔内。本研究的目的是确定吉西他滨与Y-90嵌合T84.66抗CEA抗体通过外科医生放置的导管经腹膜腔内注射而不会引起无法控制的副作用的最高剂量。这项研究的治疗预计将持续大约18周。在本研究治疗结束后，将对受试者的健康状况进行为期6个月的跟踪调查。发生在腹膜腔内的癌症很难治疗。目前的治疗方法包括化疗，通常是静脉注射。静脉化疗很难触及腹膜腔内的肿瘤。虽然静脉化疗可以产生抗肿瘤的效果，但总的来说，这些疗法是不能治愈的。抗体是一种由白细胞产生的天然蛋白质物质，用于对抗感染。它们能够识别体内的各种物质，并将其“粘住”。癌胚抗原是一种无毒物质，由某些类型的癌症制成，在大多数正常组织中没有发现。当抗CEA抗体与Y-90“放射性标记”产生Y-90嵌合T84.66抗CEA抗体时，它能够直接对产生CEA的癌症进行治疗剂量的辐射，同时避开正常组织。当这种放射性标记的抗体被ip时，更多的抗体可以到达腹膜腔内的癌症。在先前对IP Y-90嵌合T84.66抗CEA抗体的研究中，15名受试者接受了5种不同剂量水平的治疗，仅有很小的副作用。一半的受试者表现出一定程度的抗肿瘤作用。前次研究中使用的最高剂量水平将在当前研究中使用。吉西他滨是一种化疗药物，对各种实体肿瘤有效，也能使肿瘤对放射治疗更敏感。希望吉西他滨和Y-90嵌合T84.66抗CEA抗体联合使用能使各自的治疗更有效。先前的医学经验表明，当给予吉西他滨ip时，受试者可以耐受较高浓度的吉西他滨。这项研究将确定IP Y-90嵌合T84.66抗CEA抗体可以给予的最高剂量的吉西他滨，而不会对主要包含在腹膜腔内的癌症患者造成无法控制的副作用。

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. Subjects with an advanced cancer that produces a non-toxic substance called CEA (carcinoembryonic antigen) that is mostly confined to the peritoneal cavity will be asked to participate in this study. The purpose of this study is to determine the highest dose of gemcitabine that can be given without causing unmanageable side effects when combined with Y-90 Chimeric T84.66 Anti-CEA Antibody injected intraperitoneally through a catheter placed by a surgeon. Treatment on this study is expected to last approximately 18 weeks. After treatment on this study is over, subject's medical condition will be followed on this study for 6 months. Cancer occurring within the peritoneal cavity is difficult to treat. Current treatment involves chemotherapy that is delivered usually intravenously. Intravenous chemotherapy can have difficulty in reaching tumors that are within the peritoneal cavity. Although intravenous chemotherapy can result in anti-tumor effects, these therapies are, in general, not curative. Antibodies are natural protein substances produced by white blood cells to fight infection. They are able to recognize various substances in the body and "stick" to them. Carcinoembryonic antigen is a non-toxic substance made by some types of cancer that is not found in most normal tissues. When anti-CEA Antibody is "radiolabeled" with Y-90 to create Y-90 Chimeric T84.66 Anti-CEA Antibody, it is able to take a treatment dose of radiation directly to CEA-producing cancer while avoiding normal tissue. When this radiolabeled antibody is given IP, more antibody can reach cancer in the peritoneal cavity. In a previous study of IP Y-90 Chimeric T84.66 Anti-CEA Antibody, 15 subjects were treated at five different dose levels with only minor side effects. Half of the subjects showed some degree of anti-tumor effects. The highest dose level used in the previous study will be used in the current study. Gemcitabine is a chemotherapy drug that is active against various solid tumors and is also able to make tumors more responsive to radiation treatment. It is hoped that using gemcitabine and Y-90 Chimeric T84.66 Anti-CEA Antibody together will make each treatment more effective. Previous medical experience suggests that subjects can tolerate higher concentrations of gemcitabine when it is given IP. This study will determine the highest dose of IP gemcitabine that can be given with IP Y-90 Chimeric T84.66 Anti-CEA antibody without causing unmanageable side effects to subjects with cancer mostly contained in the peritoneal cavity.