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 没有治疗的月份。 大多数患者不是手术候选人。 FDA批准的治疗。 Cabozantinib和Ramucirumab显示出临床功效。 增量生存益处仅限于3-4个蒙特，大多数新疗法只能用于患者 需要保留的肝功能。 在第一，第二或第三行治疗后，患有肝功能明显的患者的疾病。 Therabionic Inc.开发了治疗P1，振幅调制（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，耗尽了所有治疗性床位。 系统由带有天线（患者勺子）的RF EMF发电机组成，该发电机放置在非 - 手术在患者的嘴里（27.12 MHz） 频率，全身吸收的结果。 疾病超过6个月。 分别是三个部分，并且耐受良好的治疗 治疗P1已被允许在美国同情使用，并获得了FDA突破设备 当Allse失败时，欧洲的指定（BDD）和认证 该SBIR直接指向II期建议的目的是收集有关与AM总体生存的疗效数据 HABE失败或不容忍至少两种以前的系统疗法的RF EMF，目标 扩大适应症，包括用作标准的第三道治疗。 治疗性P1 AM RF EMF在晚期HCC患者中。 在纪念斯隆 - 凯特癌癌症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 Benson博士，III，MD CO-I）和Mayo Clinic Cancer Center（博士 Tanios S. Bekaii-Sab，Co-i），每个手臂随机1：1随机1：1（AM RF EMF的治疗臂， 带有未建模的RF EMF的安慰剂组） 主要目标是估计总体生存（OS）。 （PFS），总体答复率（ORR），患者参与/公司率，安全性（不良事件），容忍度 （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。