Randomized phase II study of TheraBionic in advanced hepatocellular carcinoma

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.Hepatocellular carcinoma (HCC), the fastest rising cancer in the United States, results in more than 29,000 deaths annually and an average 10-month survival expectation. For most advanced HCC patients, tumor resection is not an option, and limited first and second line systemic therapies increase survival by only 3-4 months. In this proposal, Therabionic conducts an efficacy and safety clinical trial of our Therabionic P1 electromagnetic (EMF) emitting device for the systemic treatment of advanced hepatocellular carcinoma with or without metastases in patients who have exhausted all treatment options; providing the first targeted systemic EMF therapy based on tumor-specific frequencies with proven anticancer activity.