A PHASE 1 PHARMACODYNAMIC STUDY OF CP-751,871 AS NEOADJUVANT BREAST CANCER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是评估CP-751,871作为早期乳腺癌患者新辅助治疗的临床潜力。这种完全人源性的单抗能与IGF-1R特异性结合以抑制细胞生长。将使用MRS和MRI在体内监测对该药物的反应，特别是通过测量胆碱作为抗肿瘤活性的早期药效学标记。这些测量将在4T系统上进行，并使用CMRR开发的方法对光谱进行处理和量化。在研究的第1天和第22天，早期乳腺癌患者将接受20毫克/公斤的CP-751,871。根据肿瘤反应，研究人员可以酌情每隔三周给予可选的额外剂量。在整个研究过程中将监测安全性和耐受性。在治疗前、第8天和第29天(+/-3天)对患者进行磁共振波谱检查。磁共振成像将在MRS时进行，以确定肿瘤大小的变化和适当的光谱体素位置。MRS将用于监测TCHO的变化，还将用于测量肿瘤的血糖水平。手术将安排在最后一剂CP-751,871剂量后21天内进行。除了MR监测外，还将分析来自初步诊断活检和外科治疗过程的肿瘤组织，以寻找与IGF-R1途径相关的基因和蛋白质，以观察CP-751,871对IGF信号途径的影响。

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 goal of this study is to evaluate the clinical potential of CP-751,871 as a neoadjuvant treatment in patients with early breast cancer. This fully human monoclonal antibody specifically binds IGF-1R to inhibit cell growth. Response to this agent will be monitored in vivo using MRS and MRI, particularly by measuring choline as an early pharmacodynamic marker of anti-tumor activity. These measurements will be performed on the 4 T system and spectra processed and quantified using methods developed at the CMRR. Early breast cancer patients will receive 20mg/kg of CP-751,871 on Days 1 and 22 of the study. Optional additional doses can be administered at three-week intervals at the discretion of the investigator based on tumor response. Safety and tolerability will be monitored throughout the study. MRS will be performed on the patients prior to treatment and on Days 8 and 29 (+/- 3 days). MRI will be performed at the time of MRS to determine changes in tumor size and for proper spectroscopy voxel placement. MRS will be used for monitoring changes in tCho and also to measure tumor glucose levels. Surgery will be scheduled within 21 days of the final CP-751,871 dose. In addition to MR monitoring, tumor tissue from primary diagnostic biopsies and from the surgical treatment procedure will be analyzed for genes and proteins related to the IGF-R1 pathway to observe the effects of CP-751,871 on the IGF signaling pathways.