Veterans Affairs seamless phase II/III randomized trial of STAndard systemic theRapy with or without PET-directed local therapy for OligoRecurrenT prostate cancer (VA STARPORT)

退伍军人事务部无缝 II/III 期 STAndard 全身治疗随机试验，有或没有 PET 定向局部治疗，用于治疗寡复发性前列腺癌 (VA STARPORT)

• 批准号: 10578677
• 负责人: Abhishek Ashok Solanki
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578677
• 关键词: Adoption; Androgen Receptor; Area; Body part; Cancer Control; Cancer Etiology; Cessation of life; Characteristics; Clinical; Clinical Trials Design; Collaborations; Combined Modality Therapy; DNA sequencing; Data; Development; Disease; Disease Outcome; Effectiveness; Eligibility Determination; Enrollment; Failure; Goals; Growth; Healthcare Systems; Hormonal; Image; Institution; Interdisciplinary Study; Local Therapy; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Metastatic Prostate Cancer; Metastatic/Recurrent; Methodology; Molecular; Mutation; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Patient Selection; Patients; Pattern; Phase; Positron-Emission Tomography; Primary Neoplasm; Progression-Free Survivals; Prostate; Prostate Cancer therapy; Quality of life; RNA; Radiation; Radiation therapy; Recurrence; Site; Systemic Therapy; Testing; Therapeutic Agents; Tumor Markers; United States Department of Veterans Affairs; Veterans; Vitelliform macular dystrophy; Widespread Disease; biomarker identification; biomarker selection; cancer diagnosis; chemotherapy; comparison control; cooperative study; cost effectiveness; curative treatments; disorder control; economic evaluation; health economics; health related quality of life; hormone therapy; improved; improved outcome; men; molecular subtypes; mortality; novel; novel therapeutics; oncology program; palliative; patient subsets; phase III trial; precision oncology; prevent; primary endpoint; programs; randomized trial; response; standard of care; targeted agent; transcriptomics; trial comparing; tumor; tumor progression

Prostate Cancer is the most commonly diagnosed cancer among Veterans, comprising 30% of new cancer diagnoses in the VA. Eighty-five percent of men present with localized prostate can- cer, which is typically treated with active surveillance or curative local therapy using surgery or radiation therapy. Unfortunately, twenty percent of Veterans undergoing curative local therapy will develop metastatic recurrence. These men typically receive palliative systemic hormonal therapy to control their disease. Despite this, over half of men will have cancer progression within 1-2 years and half will die within 5 years. Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer. First, a subset of patients has oligorecurrent disease, de- fined as 1-5 sites of metastases. These patients are hypothesized to have an intermediate clini- cal state in which ablative local therapy with surgery or radiation to all metastatic sites of dis- ease (metastasis-directed therapy; MDT) can lead to durable disease control and potentially cure in select patients. Recent Phase II randomized trials have demonstrated improved long- term progression-free survival with MDT in the absence of systemic therapy. Yet, 75% of patients receiving MDT for oligorecurrent cancer develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. This is supported by data demonstrating that earlier palliative hormonal therapy is associated with improved survival. In fact, the second approach that has been studied in recent years, is whether escalating hormonal therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves out- comes in men with metastatic prostate cancer. Multiple phase III randomized trials demonstrate that escalating hormonal therapy with these novel therapeutic agents improves progression-free survival and overall survival dramatically. Therefore, these agents have been integrated as an option into today’s standard systemic therapy (SST) for metastatic recurrence. Given the promise of MDT to induce long-term cancer control and the effectiveness of SST to prevent further cancer progression, there is an urgent need to determine whether adding MDT to SST improves disease outcomes further. The primary goal of our study is to determine if add- ing MDT improves disease control compared to SST alone in Veterans with oligorecurrent pros- tate cancer. We will conduct a multi-institutional phase II randomized trial comparing SST with or without MDT. Other goals of the study are to determine any differences in patterns of cancer progression, survival, quality of life, and the cost-effectiveness of each approach. We also will determine how RNA transcriptomic analysis and DNA sequencing of the primary tumor from the original prostate cancer diagnosis can help determine which Veterans benefit the most from MDT. We will also utilize the VA National Precision Oncology Program to sequence metastases. The trial was developed and will be conducted in collaboration with the VA Cooperative Studies Program (CSP), and represents the multidisciplinary collaboration of prostate cancer experts, MDT experts, clinical trial design experts, and Veterans. If MDT improves FFS, our study will serve as the basis to develop a definitive phase III random- ized trial that will be powered to determine if MDT improves overall survival—establishing the new standard of care.

前列腺癌是退伍军人中最常见的诊断癌症，占30% 退伍军人事务部有新的癌症诊断。85%患有局限性前列腺的男性可以- CER，通常采用积极的监测或根治性的局部治疗，使用手术或 放射疗法。不幸的是，接受局部根治疗法的退伍军人中有20% 会发生转移性复发。这些男性通常接受姑息性全身激素治疗。 治疗以控制他们的疾病。尽管如此，超过一半的男性会有癌症进展 在1-2年内，一半将在5年内死亡。 近年来，人们对两种不同的范式进行了研究，以改善男性糖尿病患者的存活率 复发转移性前列腺癌。首先，一小部分患者患有少复发疾病， 被罚款为1-5个转移部位。这些患者被假设有一个中间诊所- 在CAL状态下，局部消融治疗通过手术或放射治疗到所有转移的肿瘤部位。 EASE(转移导向治疗；MDT)可导致持久的疾病控制，并有可能 在精选的病人中治愈。最近的II期随机试验显示，长期的 在缺乏系统治疗的情况下，接受MDT治疗的患者无进展生存期。 然而，接受MDT治疗的少复发癌症患者中，75%的患者在新的区域进展， 认为需要系统治疗来治疗隐匿性转移瘤。这是有数据支持的 证明早期的姑息激素治疗与提高存活率有关。在……里面 事实上，最近几年研究的第二种方法是，荷尔蒙的升高是否 通过添加新的雄激素受体轴靶向药物或化疗改善OUT-OUT 来自患有转移性前列腺癌的男性。多个III期随机试验证明 用这些新的治疗药物升级激素治疗可以改善无进展 生存和总体生存戏剧性地。因此，这些代理已经集成为一个 选择今天的标准系统疗法(SST)来治疗转移复发。 鉴于MDT有望诱导长期癌症控制，以及SST对 为了防止癌症的进一步发展，迫切需要确定是否添加MDT 至SST可进一步改善疾病结局。我们研究的主要目标是确定ADD- 与SST相比，ING MDT改善了具有少复发优点的退伍军人的疾病控制。 泰特癌症。我们将进行一项多机构II期随机试验，比较SST和 或者不使用MDT。这项研究的其他目标是确定癌症类型的任何差异 每种方法的进展、生存、生活质量和成本效益。我们也会 确定原发肿瘤的RNA转录分析和DNA测序 最初的前列腺癌诊断有助于确定哪些退伍军人受益最大 MDT。我们还将利用退伍军人事务部国家精确肿瘤学计划对转移进行排序。 这项试验是与退伍军人事务部合作研究中心共同开发并进行的 项目(CSP)，代表前列腺癌专家的多学科合作， MDT专家、临床试验设计专家和退伍军人。 如果MDT改善了FFS，我们的研究将作为制定最终的III阶段随机- 一项旨在确定MDT是否提高总体存活率的标准化试验--建立 新的护理标准。