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.

晚期肝癌患者的平均生存时间不到6个月，不到4个月， 几个月没有治疗。肿瘤切除术是可能的第一治疗方法。但 大多数患者不是手术候选人。Atezolizumab+贝伐珠单抗是最近的一线 FDA批准的治疗。III期试验中的其他全身治疗，包括瑞戈非尼、乐伐替尼、 卡博替尼和雷莫芦单抗显示出临床功效。虽然这些新疗法提供了额外的选择， 增加的生存益处限于3 - 4个月，并且大多数新疗法仅可用于 保留肝功能。需要对这种疾病进行额外的治疗，特别是对于晚期患者。 在一线、二线或三线治疗后进展的患者以及肝功能严重受损的患者。 TheraBionic Inc. TheraBionic P1是一种调幅（AM）射频（RF） 用于晚期肝细胞癌全身治疗的电磁场（EMF）发射装置 有或无转移的患者已用尽所有治愈性治疗选择。TheraBionic P1 系统由一个RF EMF发生器和一个天线（患者勺）组成，天线放置在非接触位置。 在病人的口腔里进行手术载波频率（27.12 MHz），AM为专有肿瘤特异性 频率，导致全身吸收。在初步研究中，41例患者中有14例（34.1%） 患病6个月以上。中位无进展生存期和总生存期分别为4.4和6.7个月， 分别有3例部分缓解和1例接近完全缓解，治疗耐受性良好。的 TheraBionic P1已被允许在美国同情使用，并已获得FDA突破性设备 指定（BDD）以及CE认证在欧洲作为最后一线的治疗时，所有其他都失败了。的 本SBIR直接进入II期提案的目的是收集关于AM总生存期的疗效数据 RF EMF用于既往至少接受过两次全身治疗失败或不耐受的受试者，目标是 扩大适应症，将其作为标准的三线治疗。具体目标1： TheraBionic P1 AM RF EMF用于晚期HCC患者。我们将进行一项前瞻性、双盲、双臂 在纪念斯隆-凯特琳癌症中心进行的一项随机对照多中心试验（Ghassan Abou-Alfa博士， PI）、维克森林浸信会综合癌症中心（William Blackstock博士，共同PI）、Lurie综合 西北大学癌症中心（Al B博士）。本森，三，医学博士co-I），和马约诊所癌症中心（博士。 塔尼奥斯湾Bekaii-Saab，Co-I），162名受试者以1：1的比例随机分配至每组（AM RF EMF治疗组， 未调制RF EMF的安慰剂组）。具体目标2：主要和次要目标分析。的 主要目的是估计总生存期（OS）。次要目标包括无进展生存期 (PFS)、总缓解率（ORR）、患者参与率/依从率、安全性（不良事件）、耐受性 （研究退出率）、生活质量（EQ-5D-5L调查）以及与甲胎蛋白水平的相关性。