Rare genitourinary tumors projects

罕见泌尿生殖肿瘤项目

• 批准号: 10702756
• 负责人: Andrea Apolo
• 金额: $ 39.64万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702756
• 关键词: Adenocarcinoma; Affect; Bladder; Bladder Adenocarcinoma; Bladder Squamous Cell Carcinoma; Caring; Clinical; Clinical Research; Clinical Trials; Collecting Ducts of Bellini Carcinoma; Country; Data; Data Pooling; Disease; Duct (organ) structure; Genitourinary system; Histologic; Histology; Human; Immune; Incidence; Individual; Literature; Malignant Neoplasms; Malignant neoplasm of penis; Malignant neoplasm of testis; Malignant neoplasm of urinary bladder; Mutation; Nivolumab; Patients; Penis carcinoma; Peripheral Blood Mononuclear Cell; Persons; Pharmaceutical Preparations; Phase; Rare Diseases; Renal carcinoma; Resources; Science; Skin Appendage Carcinoma; Small Cell Carcinoma; Squamous cell carcinoma; Transitional Cell Carcinoma; Tumor Expansion; United States National Institutes of Health; Urethra; Urogenital Cancer; Variant; base; bladder Carcinoma; bone; cancer type; cohort; exome sequencing; ipilimumab; phase 1 study; phase 2 study; rare cancer; recruit; response; transcriptome sequencing; tumor; urogenital tract

A phase 2 study of Ipilimumab, CabOzantinib, and NIvolumab in rare genitourinary (GU) cancers (ICONIC) The phase 1 study of combination CaboNivo and CaboNivoIpi included patients with rare GU histologies. Objective responses were seen in patients with adenocarcinoma of the bladder/urachal, squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, penile cancer, sarcomatoid RCC, chromophobe RCC, and renal medullary carcinoma, leading to multiple rare tumor expansion cohorts. The final data for these rare tumors and the pooled data from the phase 1 and expansion cohorts are currently being analyzed. Based on these data, I initiated a phase 2 study through the Alliance cooperative group of CaboNivoIpi in patients with rare GU tumors which includes 12 cohorts: bladder squamous cell carcinoma, bladder small cell carcinoma, bladder adenocarcinoma, bladder plasmacytoid, bladder sarcomatoid, urethra (all histologies), penile cancer, sarcomatoid RCC, collecting duct RCC, renal medullary carcinoma, bone-only non-prostate GU tumor, and miscellaneous rare GU tumors. As of September 2020, the trial has accrued 100 patients (44% accrued). Preliminarily in this study we have seen confirmed responses in the bladder squamous cell carcinoma, bladder small cell carcinoma, bladder adenocarcinoma, urethra, penile cancer, sarcomatoid RCC, renal medullary carcinoma, and testicular adnexal carcinoma. An extensive number of translational correlatives are being conducted in this study with baseline and serial subsequent cycles of therapy. We will analyze the immune subsets of circulating PBMCs and ctDNA and use whole-exome sequencing to define the relationship between tumor mutational burden in each histologic subtype and response to the trial drugs. We will also use RNA sequencing to define the relationship between expression-based subtypes, the immune context of the tumors, and response to study drugs. Having a rare tumor clinical trial developed through the NIH and available nationally through a cooperative such as the Alliance builds on our center's recruitment strength and on our collaborative science. If this trial shows clinical activity, it may provide a potential new treatment option for patients with rare GU tumors.

稀有泌尿瘤（GU）癌（Iconic）的ipilimumab，cabozantinib和nivolumab的2阶段研究（标志性）的第一阶段研究结合Cabonivo和Cabonivoipi包括具有罕见的GU组织学的患者。在膀胱/尿道腺癌，膀胱的鳞状细胞癌，膀胱癌的小细胞癌，阴茎癌，肉瘤癌RCC，成相型RCC和肾脏肾癌的患者中，观察到了客观反应。目前正在分析这些稀有肿瘤的最终数据以及1阶段1和扩展队列的合并数据。 Based on these data, I initiated a phase 2 study through the Alliance cooperative group of CaboNivoIpi in patients with rare GU tumors which includes 12 cohorts: bladder squamous cell carcinoma, bladder small cell carcinoma, bladder adenocarcinoma, bladder plasmacytoid, bladder sarcomatoid, urethra (all histologies), penile cancer, sarcomatoid RCC, collecting duct RCC，肾脏髓瘤，仅骨骼的非肉食肿瘤和其他稀有的GU肿瘤。截至2020年9月，该试验累积了100名患者（44％的患者）。在这项研究中，我们看到了膀胱鳞状细胞癌，膀胱小细胞癌，膀胱腺癌，尿道，阴茎癌，肉瘤性RCC，肾脏髓质癌和睾丸adnexal癌的反应。这项研究正在使用基线和随后的治疗周期进行大量翻译相关性。我们将分析循环PBMC和ctDNA的免疫子集，并使用全外例测序来定义每个组织学亚型中肿瘤突变负担与试验药物的反应之间的关系。我们还将使用RNA测序来定义基于表达的亚型，肿瘤的免疫背景和对研究药物的反应之间的关系。 通过NIH开发了罕见的肿瘤临床试验，并通过联盟等合作社在全国范围内获得，建立在我们中心的招聘力量和我们的协作科学的基础上。如果该试验显示临床活动，则可能为患有罕见GU肿瘤的患者提供潜在的新治疗选择。