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

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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.