Translational Research Studies in Clinical Trials of Novel Therapeutics for Sarco

Sarco 新型疗法临床试验的转化研究

• 批准号: 7942979
• 负责人: GARY K SCHWARTZ
• 金额: $ 118.44万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7942979
• 关键词: Accounting; Affect; Aftercare; Antibodies; BAY 54-9085; Basic Science; Biological; Biopsy; CCI-779; Cancer Family; Cancer Therapy Evaluation Program; Cartilage; Cessation of life; Child; Clinical; Clinical Research; Clinical Trials; Collaborations; Connective Tissue; Correlative Study; Cytotoxic agent; Data; Dermatofibrosarcoma Protuberans; Disease; Drug Combinations; Enrollment; Epithelial Cells; Erinaceidae; Ewings sarcoma; Fatty acid glycerol esters; Funding; Funding Opportunities; Gastrointestinal Stromal Tumors; Hemangiosarcoma; Heterogeneity; Histology; IGF1 gene; Incidence; Institution; Insulin-Like-Growth Factor I Receptor; Laboratory Research; Lead; Malignant Neoplasms; Metastatic/Recurrent; Monoclonal Antibodies; Muscle; Nature; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phosphotransferases; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor Receptor; Proteins; Public Health; Recurrence; Research; Screening procedure; Software Tools; Teenagers; Testing; Tissues; Translational Research; United States; Vascular Endothelial Growth Factor Receptor; age group; base; bone; evidence base; gamma secretase; improved; inhibitor/antagonist; insight; interest; mTOR Inhibitor; notch protein; novel; novel strategies; novel therapeutics; phase 2 study; public health relevance; receptor; research study; response; sarcoma; smoothened signaling pathway; tumor; young adult

DESCRIPTION (provided by applicant): The 20% rarest cancers account for approximately 35% of the deaths from cancer in the United States. As a result, a better understanding of the nature of these rare tumors is in the public health's best interest. We study sarcomas, rare cancers of connective tissue: bone, muscle, fat, cartilage, and the other tissues that hold us together. These are cancers that occur disproportionately in children, teens, and young adults, although different forms affect different age groups. In all, sarcomas account for less than 1% of all cancer in the United States. However, since they can arise from so many different tissues, there are 70 or more sarcoma subtypes. We are interested in finding new treatments for the people with these rare cancers, who do not benefit from research on more common cancers. We have identified two new combinations of drugs that may be useful for people with sarcoma. The first of these is A12, an "insulin-like growth factor 1 receptor" inhibitor, and temsirolimus, an mTOR inhibitor. The second is a blocker of Hh (hedgehog) signaling, GDC-0449, which we are combining with a blocker of gamma secretase (RO4929097) [Notch pathway] in a novel study for people with recurrent sarcomas. We are seeking funding to perform this multi-center study, focusing on biopsies from patients on these two studies for biological correlates of blockade of these various pathways. These biopsies will help us determine would or would not benefit from such therapy. We will also use a software tool we have recently developed, called StudyTracker, to collect the data from the multiple participating centers on the GDC-0449/RO4929097 phase I-II study. With this information, we will be able to use tests of tumors to insure that the right person is receiving the right medication, with the best chance of getting a good result from that treatment. Without such testing, clinical trials are reduced to "throwing darts"-some people could benefit, but we will not understand why. This approach should lead to new and efficient means to treat patients with sarcomas and may also impact patients with more common cancers. PUBLIC HEALTH RELEVANCE: This is a project to support correlative studies for two multicenter clinical trials of new drugs for patients with sarcomas. These novel approaches will improve the treatment options for this underserved group of patients with this rare family of cancers

描述（由申请人提供）：在美国，20%最罕见的癌症占癌症死亡人数的约35%。因此，更好地了解这些罕见肿瘤的性质符合公共卫生的最佳利益。我们研究肉瘤，一种罕见的结缔组织癌症：骨骼，肌肉，脂肪，软骨和其他将我们连接在一起的组织。这些癌症不成比例地发生在儿童，青少年和年轻人中，尽管不同的形式影响不同的年龄组。在美国，肉瘤占所有癌症的不到1%。然而，由于它们可以来自许多不同的组织，因此有70种或更多的肉瘤亚型。我们有兴趣为患有这些罕见癌症的人找到新的治疗方法，这些人无法从更常见的癌症研究中受益。我们已经确定了两种新的药物组合，可能对肉瘤患者有用。其中第一个是A12，一种“胰岛素样生长因子1受体”抑制剂，和temsirolimus，一种mTOR抑制剂。第二种是Hh（hedgehog）信号传导阻滞剂GDC-0449，我们在一项针对复发性肉瘤患者的新研究中将其与γ分泌酶（RO 4929097）[Notch途径]阻滞剂结合使用。我们正在寻求资金来进行这项多中心研究，重点是这两项研究中患者的活检，以了解这些不同途径阻断的生物学相关性。这些活检将帮助我们确定是否会从这种治疗中受益。我们还将使用我们最近开发的一种名为StudyTracker的软件工具，从GDC-0449/RO 4929097 I-II期研究的多个参与中心收集数据。有了这些信息，我们将能够使用肿瘤的测试，以确保正确的人正在接受正确的药物治疗，并有最好的机会从该治疗中获得良好的结果。如果没有这样的测试，临床试验就变成了“掷飞镖”--有些人可能会受益，但我们不明白为什么。这种方法应该导致新的和有效的手段来治疗肉瘤患者，也可能影响更常见的癌症患者。 公共卫生相关性：这是一个支持两项肉瘤患者新药多中心临床试验相关研究的项目。这些新方法将改善这一罕见癌症家族患者的治疗选择

项目成果

Primary angiosarcoma of bone: a retrospective analysis of 60 patients from 2 institutions.

• DOI: 10.1097/coc.0b013e31827defa1
• 发表时间: 2014-12
• 期刊: American journal of clinical oncology
• 作者: Palmerini E;Maki RG;Staals EL;Alberghini M;Antonescu CR;Ferrari C;Ruggieri P;Mavrogenis A;Bertoni F;Cesari M;Paioli A;Marchesi E;Picci P;Ferrari S
• 通讯作者: Ferrari S