Randomized phase II study of TheraBionic in advanced hepatocellular carcinoma

TheraBionic 治疗晚期肝细胞癌的随机 II 期研究

• 批准号: 10254967
• 负责人: Valerie Pasche
• 金额: $ 105.91万
• 依托单位: THERABIONIC INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10254967
• 关键词: Adverse event; BAY 54-9085; Baptist Church; Blood Tests; Cancer Etiology; Categories; Certification; Cessation of life; Child; Clinical Trials; Comprehensive Cancer Center; Coupled; Data; Devices; Disease; Double-Blind Method; Effectiveness; Electromagnetic Fields; Electromagnetics; Enrollment; Europe; Excision; FDA approved; Frequencies; Goals; Impairment; In complete remission; Intervention; Label; Lead; Legal patent; Liver Cirrhosis; Malignant Neoplasms; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; Neoplasm Metastasis; New Agents; Nivolumab; Oral cavity; Participant; Patient Participation; Patients; Phase; Placebos; Primary Neoplasm; Primary carcinoma of the liver cells; Prognosis; Progression-Free Survivals; Quality of life; Randomized; Safety; Small Business Innovation Research Grant; Stable Disease; Surveys; System; Systemic Therapy; Therapeutic; Therapeutic Intervention; Time; Toxic effect; United States; Universities; Withdrawal; absorption; advanced disease; alpha-Fetoproteins; anticancer activity; arm; base; bevacizumab; clinical efficacy; curative treatments; exhaust; expectation; forest; improved; inhibitor/antagonist; ipilimumab; liver function; liver preservation; multi-site trial; novel therapeutics; pembrolizumab; phase 2 study; phase III trial; prospective; radio frequency; response; treatment arm; tumor

The average survival time of patients suffering from advanced HCC is less than six months, less than four- months without treatment. Tumor resection is the first therapeutic approach when possible. However, the majority of patients are not surgical candidates. Atezolizumab+bevacizumab is the most recent first-line treatment approved by the FDA. Other systemic therapies in Phase III trials, including regorafenib, lenvatinib, cabozantinib, and ramucirumab, show clinical efficacy. While these new therapies provide additional options, incremental survival benefits are limited to 3-4 months and most new therapies can only be used in patients with preserved liver function. Additional therapies for this disease are needed, especially for patients with advanced disease who progress after first, second, or third line therapy and for those with severely impaired liver function. TheraBionic Inc. has developed the TheraBionic P1, an amplitude modulated (AM) radiofrequency (RF) electromagnetic field (EMF) emitting device for the systemic treatment of advanced hepatocellular carcinoma with or without metastases in patients who have exhausted all curative treatment options. The TheraBionic P1 system consists of an RF EMF generator, coupled with an antenna (patient spoon), which is placed non- surgically in the patient’s mouth. A carrier frequency (27.12 MHz), with AM at proprietary tumor-specific frequencies, results in whole-body absorption. In preliminary studies, 14 out of 41 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival and overall survival were 4.4 and 6.7 months, respectively. There were three partial and one near complete responses with treatment well tolerated. The TheraBionic P1 has been allowed for compassionate use in the U.S. and has received FDA Breakthrough Device Designation (BDD) as well as CE certification in Europe as a last line of treatment when all else has fails. The objective of this SBIR Direct to Phase II proposal is to gather efficacy data concerning overall survival with AM RF EMF in subjects who have failed or are intolerant to at least two previous systemic therapies, with the goal of expanding indications to include use as a standard third line of treatment. Specific Aim 1: Clinical trial of TheraBionic P1 AM RF EMF in advanced HCC patients. We will conduct a prospective, double-blind, two-arm randomized controlled multi-site trial at Memorial Sloan-Kettering Cancer Center (Dr. Ghassan Abou-Alfa, lead PI), Wake Forest Baptist Comprehensive Cancer Center (Dr. William Blackstock, co-PI), Lurie Comprehensive Cancer Center of Northwestern University (Dr. Al B. Benson, III, MD co-I), and Mayo Clinic Cancer Center (Dr. Tanios S. Bekaii-Saab, Co-I) with 162 subjects randomized 1:1 to each arm (treatment arm with AM RF EMF, placebo arm with unmodulated RF EMF). Specific Aim 2: Primary and secondary objective analyses. The primary objective is to estimate overall survival (OS). Secondary objectives include progression-free survival (PFS), overall response rate (ORR), patient participation/compliance rates, safety (adverse events), tolerability (study withdrawal rates), quality of life (EQ-5D-5L survey), and correlation with alpha-fetoprotein levels.

患有晚期HCC患者的平均生存时间少于六个月，小于四个月 几个月没有治疗。肿瘤切除是可能的第一种治疗方法。但是， 大多数患者不是手术候选者。 Atezolizumab+bevacizumab是最新的一线 FDA批准的治疗。 III期试验中的其他全身疗法，包括雷诺非尼，伦瓦替尼， Cabozantinib和Ramucirumab显示出临床效率。尽管这些新疗法提供了其他选择，但 增量生存益处限制为3-4个月，大多数新疗法只能用于患者 保留的肝功能。需要针对这种疾病的其他疗法，尤其是对于晚期患者 在第一，第二或第三线治疗以及肝功能严重受损的疾病之后进展的疾病。 Therabionic Inc.开发了治疗P1，这是一个放大器调制（AM）射频（RF） 电磁场（EMF）发射装置，用于全身治疗晚期肝细胞癌 有或没有转移的患者，耗尽所有治疗方法的患者。治疗P1 系统由RF EMF发生器组成，并与天线（患者勺子）相结合，该发电机放置在非 - 手术在患者的嘴里。载体频率（27.12 MHz），AM处于专有肿瘤特异性 频率，导致全身滥用。在初步研究中，41例患者中有14例（34.1％）稳定 疾病超过6个月。中位无进展生存期和总生存期为4.4和6.7个月， 分别。有三个部分和一个几乎完整的反应，可耐受治疗。 治疗P1已被允许在美国同情使用，并获得了FDA突破设备 当其他所有问题失败时，欧洲的名称（BDD）和CE认证是最后一系列的治疗方法。这 该SBIR直接直接提出II期建议的目的是收集有关与AM的总体生存的效率数据 在失败或不容忍至少两种以前的全身疗法的受试者中的RF EMF，目标 扩展的适应症，包括用作标准的第三道治疗。特定目标1：临床试验 晚期HCC患者的治疗性P1 AM RF EMF。我们将进行前瞻性，双盲的两臂 纪念斯隆 - 凯特林癌症中心的随机对照多站点试验（Ghassan Abou-Alfa博士，Lead PI），Wake Forest Baptist综合癌症中心（William Blackstock博士，Co-Pi），Lurie综合 西北大学癌症中心（Al B. Benson博士，III，MD CO-I）和Mayo Clinic Cancer Center（博士 Tanios S. Bekaii-saab，Co-I），每个手臂随机1：1随机1：1（AM RF EMF的治疗臂， 安慰剂臂，带有未调制的RF EMF）。特定目标2：主要和次要客观分析。这 主要目的是估计总体生存（OS）。次要目标包括无进展的生存 （PFS），总体答复率（ORR），患者参与/合规率，安全性（不良事件），耐受性 （研究提取率），生活质量（EQ-5D-5L调查）以及与α-竞争蛋白水平的相关性。