iCAN-PREVENT: MD Anderson International Cancer Prevention Clinical Trial Consortium

摘要 与癌症相关的死亡是美国第二大最常见的死亡原因，也是最常见的 减少癌症相关死亡和癌症发病率的有希望的策略是通过癌症 预防。以前的临床试验已经证明了用药预防癌症的可行性。 疫苗或癌症预防药物。然而，这些药物的使用受到限制，因为它们的 副作用。显然，更安全、更有效的癌症预防干预措施是 对于健康的个人来说，迫切需要一种可接受的方法。因此，这一计划的首要目标是 应用程序是将基础、翻译和临床研究人员团队聚集在一起，以确定 预防癌症的新策略，在癌症预防临床试验中进行测试，并最终 将安全、有效和可接受的预防疗法广泛应用于个人- 这种疾病的风险。为了实现这一目标，我们成立了一个国际财团(ICAN- 预防联盟)由癌症预防专家、临床试验专家、分子 生物学家、翻译研究人员、病理学家、统计学家和生物信息学专家 开发和进行早期癌症预防试验。我们的临床研究团队拥有庞大的 有进行早期和晚期临床试验的经验，并已进行了18个阶段的临床试验 和II癌症预防临床试验通过我们之前的化学预防临床试验 财团。在这里，我们提出了两个目的来检验我们可以进行药物试验的假设 和疫苗疗法，并证明这些预防性疗法将安全地调节 关键的肿瘤促进途径。这些早期临床试验的结果将支持 将这些干预措施推进到第三阶段测试，并最终支持FDA的批准 这些预防癌症的干预措施。我们将进行5至10项早期临床试验 测试一系列有希望的癌症预防药物，疫苗和 对癌症高危人群的免疫调节干预，以及2)开发和 实施新方法，加强预防试验中患者的招募和留住 使用社交媒体、电子新闻和移动消息。展示我们的能力 为了开发新的癌症预防试验，我们提供了两个样本试验：一种新的I期试验 编码Lynch患者体内新移码抗原的DNA疫苗 综合症，以及测试mTOR抑制剂伊波利莫斯改变乳房的能力的第二阶段试验 既往三阴性乳腺癌患者的组织生物标记物。这些研究的结果 早期试验将推进癌症预防药物的开发，并最终将有所帮助 通过预防降低癌症发病率和死亡率。

Abstract Cancer-related death is the second most common cause of death in the US, and the most promising strategy to reduce cancer-related deaths and cancer incidence is through cancer prevention. Previous clinical trials have demonstrated the feasibility of preventing cancer using vaccines or cancer preventive drugs. However, the use of these agents is limited due to their side effects. Clearly, safer and more effective cancer prevention interventions that are acceptable to healthy individuals are urgently needed. Thus, the overarching goal of this application is to bring a team of basic, translational, and clinical researchers together to identify novel strategies to prevent cancer, test them in cancer prevention clinical trials, and ultimately bring safe, efficacious, and acceptable preventive therapies to general use in individuals at high- risk of this disease. To achieve this goal, we formed an international consortium (the iCAN- PREVENT consortium) comprised of cancer prevention experts, clinical trialists, molecular biologists, translational researchers, pathologists, statisticians, and bio-informatics experts, to develop and conduct early phase cancer prevention trials. Our clinical research team has vast experience in conducting both early and late phase clinical trials, and has conducted 18 Phase I and II cancer prevention clinical trials through our previous chemoprevention clinical trial consortia. Here, we propose two aims to test the hypothesis that we can conduct trials of drug and vaccine therapies and demonstrate that these preventive therapies will safely modulate critical tumor promoting pathways. Results from these early phase clinical trials will support the advancement of these interventions to Phase III testing, and ultimately support the FDA-approval of these interventions for cancer prevention. We will 1) conduct 5 to 10 early phase clinical trials testing the safety and activity of a series of promising cancer prevention drugs, vaccines, and immune modulating interventions in individuals at high-risk of cancer, and 2) develop and implement novel methods to enhance recruitment and retention of patients in prevention trials using social media, electronic news-blasts, and mobile messaging. To demonstrate our ability to develop novel cancer prevention trials, we provide two sample trials: a Phase I trial of a novel DNA-based vaccine encoding novel frameshift antigens that develop in individuals with Lynch Syndrome, and a Phase II trial testing the ability of the mTOR inhibitor everolimus to alter breast tissue biomarkers in individuals with prior triple-negative breast cancer. The results of these early phase trials will advance cancer prevention drug development, and will ultimately help reduce cancer incidence and mortality through prevention.