UAB 9846 PHASE I TRIAL OF 131I-HUCC49DCH2 FOR COLON CANCER

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。在转移性或不可切除的结肠癌或直肠癌患者中，本研究的目的是：(1)确定静脉注射（IV） 131I-HuCC49ΔCH2（缺失CH2区域的重组人源化小鼠CC49抗体）的最大耐受剂量（MTD）；(2)测定IV 131I-HuCC49&#916；CH2的毒性、血浆药代动力学、全身生物分布及结合稳定性；(3)测定131I-HuCC49&#916；CH2对肿瘤部位的定位能力（测定对肿瘤、正常器官和全身的剂量学估计）；(4)表征人对131I-HuCC49&#916；CH2的免疫反应，并确定两次输注治疗的可行性。前瞻性参与者将进行初步测试，以确定他们是否有资格参加本研究。第一组患者将接受10 mCi 131I-HuCC49&#916；CH2作为诊断/剂量学研究。一旦获得该组的剂量学信息，将为后续组确定治疗起始剂量水平。抗体输注当日密切观察患者是否有过敏反应。为了确定抗体是否与癌细胞结合，在治疗后的第一周将进行几次专门的扫描；将收集血液样本以确定对血细胞和器官功能的影响，以及抗体以确定系统中的抗体水平。每隔6个月对患者进行为期两年的随访。

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. The objectives of this study in patients with metastatic or unresectable colon or rectal cancer, are to: (1) determine the maximum tolerated dose (MTD) of intravenous (IV) 131I-HuCC49ΔCH2 (recombinant humanized murine CC49 antibody with a deleted CH2 region); (2) determine the toxicities, the plasma pharmacokinetics, whole body biodistribution and conjugate stability of IV 131I-HuCC49ΔCH2; (3) determine the ability of 131I-HuCC49ΔCH2 to localize to tumor sites (dosimetry estimates to tumor, normal organs and whole body will be determined); and (4) characterize the human immune response against 131I-HuCC49ΔCH2 and determine the feasibility of administering two treatment infusions. Perspective participants will have preliminary tests conducted to determine their eligibility for enrollement in the study. The first group of patients will receive 10 mCi 131I-HuCC49ΔCH2 as a diagnostic/dosimetry study. Once dosimetry information from this group is obtained, the therapeutic starting dose level will be established for subsequent groups. On the day of antibody infusion, the patient will be closely observed for allegic reaction. To determine whether the antibody has bound to cancer cells, several specialized scans will be conduted during the first week after treatment; blood samples will be collected to determine the effects on blood cells and organ function as well the antibody to determine the antibody levels in the system. Patients will be followed at 6-month intervals for up to two years.