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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。将要求患有晚期癌症的受试者参与本研究，该晚期癌症产生称为CEA（癌胚抗原）的无毒物质，该物质主要局限于腹膜腔。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腹膜内注射时，可以给予而不会引起无法控制的副作用的最高剂量。本研究的治疗预计持续约18周。本研究治疗结束后，将对受试者的医疗状况进行为期6个月的随访。 发生在腹腔内的癌症是很难治疗的，目前的治疗方法是静脉化疗。静脉化疗可能难以到达腹膜腔内的肿瘤。虽然静脉化疗可以产生抗肿瘤作用，但这些疗法通常不能治愈。抗体是由白色血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“粘”在它们身上。癌胚抗原是由某些类型的癌症产生的无毒物质，在大多数正常组织中不存在。当抗CEA抗体用Y-90“放射性标记”以产生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，同时避免正常组织。当IP给予这种放射性标记的抗体时，更多的抗体可以到达腹膜腔中的癌症。在IP Y-90嵌合T84.66抗CEA抗体的先前研究中，15名受试者以五种不同剂量水平治疗，仅具有轻微副作用。一半的受试者显示出一定程度的抗肿瘤作用。本研究将使用既往研究中使用的最高剂量水平。吉西他滨是一种化疗药物，对各种实体瘤有活性，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抗体联合使用将使每种治疗更有效。既往医学经验表明，IP给药时，受试者可耐受较高浓度的吉西他滨。本研究将确定IP吉西他滨的最高剂量，该剂量可与IP Y-90嵌合T84.66抗CEA抗体一起给药，而不会对大多数癌症位于腹膜腔的受试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.