Cancer Therapy Trials using novel vaccine platforms

使用新型疫苗平台进行癌症治疗试验

• 批准号: 8763429
• 负责人: Ravi Madan
• 金额: $ 5.03万
• 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/8763429
• 关键词: Calcitonin; Cancer Patient; Cancer Vaccines; Clinical; Data; Disease; Enrollment; Evaluable Disease; FDA approved; Goals; Growth; Heating; Human; Immune; Immune response; Immunologics; Indolent; Kinetics; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Metric; Myelogenous; Natural Killer Cells; Outcome; Patients; Population; Process Measure; Progressive Disease; Proteins; Randomized; Reaction Time; Recombinant Vaccines; Recombinants; Regulatory T-Lymphocyte; Saccharomyces cerevisiae; Safety; Schedule; Serum; Site; Suppressor-Effector T-Lymphocytes; T-Lymphocyte; Therapeutic; Time; Toxic effect; Tumor Burden; Vaccines; Visit; Yeasts; arm; base; cancer therapy; killings; medullary thyroid carcinoma; novel; novel vaccines; patient population; peripheral blood; phase 1 study; phase 2 study; response; tumor growth; vaccine efficacy

Saccharomyces cerevisiae (yeast) has been genetically modified to express CEA protein and employed as a heat-killed immune-stimulating, therapeutic cancer vaccine (GI-6207). A previous phase I study with GI-6207 demonstrated safety, bio-marker stabilization and enhanced immune response in some patients. CEA is over-expressed in multiple malignancies, including medullary thyroid cancer (MTC). The recently FDA-approved therapies for metastatic MTC (vandetanib, cabozantinib) come with significant toxicity and are reserved for symptomatic/progressive disease. There is a large population of asymptomatic MTC patients with small tumor burden and/or disease that remains indolent. The standard management of these patients is observation. Preliminary data suggest that tumor growth rate (as measured by CEA and calcitonin) is a quantifiable variable within a 3-6 month time-frame. Retrospective data from prostate cancer studies suggest that vaccines can alter growth rates within 3-4 months. We hypothesize that GI-6207 can alter tumor growth rate in this asymptomatic, indolent MTC patient population, and potentially impact long term outcome. A phase 2 study at the NCI will evaluate the effect of GI-6207 on calcitonin growth rates in metastatic MTC. 34 patients with minimally symptomatic, radiographically-evaluable, metastatic MTC will be randomized 1:1. Arm A will receive vaccine for a year from the time of enrollment. Arm B will receive the same schedule vaccine after a period of 6 months of surveillance. GI-6207 will be administered subcutaneously at 4 sites at 10 yeast units/site, every 2 weeks for 7 visits (day 1, 15, 29, 43, 57, 71, 85), then monthly up to 1 year of treatment. The primary end point will compare the effect of GI-6207 on calcitonin growth rate kinetics between the vaccine and surveillance arms at 6 months. Secondary end points include immunologic responses (CEA-specific T cells, effector/regulatory T-cell ratio, natural killer cells, myeloid derived suppressor cells) objective responses, time to progression, and changes in CEA kinetics. If this trial can prospectively demonstrate that vaccines can alter tumor growth rate, and such changes are associated with clinical outcomes, then changes in tumor growth rate may become a clinical metric to evaluate vaccine efficacy in MTC and other populations. The study opened in March of 2013 and 8 patients have been enrolled.

酿酒酵母（酵母）经过基因改造，可表达 CEA 蛋白，并用作热灭活的免疫刺激治疗性癌症疫苗 (GI-6207)。此前一项 GI-6207 的 I 期研究证明了 GI-6207 的安全性、生物标志物稳定性以及某些患者的免疫反应增强。 CEA 在多种恶性肿瘤中过度表达，包括甲状腺髓样癌 (MTC)。最近 FDA 批准的转移性 MTC 疗法（凡德他尼、卡博替尼）具有显着的毒性，仅用于有症状/进展性疾病。有大量无症状 MTC 患者肿瘤负荷较小和/或疾病仍处于惰性状态。这些患者的标准管理是观察。初步数据表明，肿瘤生长率（通过 CEA 和降钙素测量）是 3-6 个月时间范围内的一个可量化变量。前列腺癌研究的回顾性数据表明，疫苗可以在 3-4 个月内改变生长速度。我们假设 GI-6207 可以改变无症状、惰性 MTC 患者群体的肿瘤生长速度，并可能影响长期结果。 NCI 的一项 2 期研究将评估 GI-6207 对转移性 MTC 中降钙素生长速率的影响。 34 名症状轻微、可通过影像学评估的转移性 MTC 患者将以 1:1 的比例进行随机分配。 A 组将从注册之日起接种一年的疫苗。 B 组将在 6 个月的监测期后接种相同时间表的疫苗。 GI-6207 将在 4 个部位皮下注射，每部位 10 个酵母单位，每 2 周一次，共 7 次就诊（第 1、15、29、43、57、71、85 天），然后每月一次，直至治疗 1 年。主要终点将比较 6 个月时 GI-6207 对疫苗组和监测组之间降钙素生长速率动力学的影响。次要终点包括免疫反应（CEA特异性T细胞、效应/调节性T细胞比率、自然杀伤细胞、骨髓源性抑制细胞）客观反应、进展时间和CEA动力学变化。如果这项试验能够前瞻性地证明疫苗可以改变肿瘤生长速率，并且这种变化与临床结果相关，那么肿瘤生长速率的变化可能成为评估 MTC 和其他人群中疫苗功效的临床指标。该研究于 2013 年 3 月开始，已入组 8 名患者。