NOVARTIS CAUY922A2101: A PHASE I DOSE ESCALATION, MULTI-CENTER, OPEN-LABEL STUDY

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。 具体目标： 主要目标--剂量递增臂 在对患有晚期实体肿瘤的成年患者进行每周一次的静脉注射时，确定AUY922作为单一药物的MTD，这些患者尽管接受标准治疗，但病情仍在发展，或者没有标准治疗。 主要目标-乳腺癌剂量扩展臂 在MTD上，将进一步扩展两个手臂，以评估以下乳腺癌患者群体的反应(根据两阶段多项设计)： 1.HER2阳性、不能手术的局部晚期或转移性乳腺癌患者必须： 1.曲妥珠单抗耐药史，定义为局部或全身性疾病进展，接受至少8周的曲妥珠单抗方案治疗。 2.之前接受了至少1个但不超过2个基于抗HER2的方案，包括至少1个包含曲妥珠单抗的方案。(在接受佐剂或新佐剂曲妥珠单抗治疗期间发生转移的患者符合条件) 2.ER阳性、不能手术的局部晚期或转移性乳腺癌患者，接受内分泌治疗的标准序列，且其疾病已在至少一条针对晚期疾病的内分泌治疗路线上进展。

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. SPECIFIC AIMS: Primary objective - dose escalation arm " To determine the MTD of AUY922 as a single agent when administered IV on a once weekly schedule to adult patients with advanced solid tumors, whose disease has progressed despite standard therapy or for whom no standard therapy exists. Primary objective - breast cancer dose expansion arm " At the MTD two further arms will be expanded to assess response (according to a two stage multinomial design) in the following breast cancer patient populations: 1. Patients with HER2 positive non-operable locally advanced or metastatic breast cancer must have: 1. History of trastuzumab resistance, defined as either local or systemic disease progression on treatment with at least 8 weeks of a trastuzumab containing regimen. 2. Received at least 1 but no more than 2 prior anti HER2 based regimens including at least 1 regimen containing trastuzumab. (Patients who develop metastases while receiving adjuvant or neo-adjuvant trastuzumab are eligible) 2. Patients with ER positive non-operable locally advanced or metastatic breast cancer who received standard sequence lines of endocrine therapy and whose disease has progressed on at least one line of endocrine therapy for advanced disease.