Electromagnetic Fields Versus Placebo For Child-Pugh A and B Patients With Advanced Hepatocellular Carcinoma (ARTEMIS)

A Randomized Study of Intrabucally Administered Electromagnetic Fields Versus Placebo for Patients With Child-Pugh A or B With Advanced Hepatocellular Carcinoma

The primary goals of this study are to compare overall survival and quality of life in subjects with Child-Pugh A or B advanced hepatocellular carcinoma when treated with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Device: TheraBionic Device; Device: Quality of Life Assessment; Device: Placebo Device

Detailed Description

Primary Objectives

To compare the overall survival between subjects with advanced hepatocellular carcinoma treated either with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

To compare the patient-reported disease-related symptoms between subjects with advanced hepatocellular carcinoma treated either with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

Secondary Objectives

To compare progression-free survival between subjects treated either with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

To compare safety and tolerability between subjects treated either with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

To compare the effect on levels of alpha-fetoprotein between subjects treated either with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

To compare global treatment side effect bother between subjects treated either with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

To compare patient-rated symptomatic adverse events between subjects treated either with a device emitting radiofrequencies modulated at specific frequencies or with a device emitting unmodulated radiofrequencies.

• Study Type: Interventional
• Enrollment (Estimated): 166
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Valerie K Pasche, MD; Phone Number: 3129610168; Email: valerie.pasche@therabionic.com
• Study Contact Backup: Name: Boris C Pasche, MD, PhD; Phone Number: 3122864703; Email: boris.pasche@therabionic.com

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • Not yet recruiting
      • Tampa General Hospital, Tampa General Cancer Center
      • Contact: Principal Investigator; Email: andreask@usf.edu
      • Principal Investigator: Andreas Karachristos, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
      • Contact: Al B Benson, MD; Email: albenson@nm.org
      • Principal Investigator: Al Benson, MD
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Comprehensive Cancer Center
      • Contact: Study Nurse; Email: snmoore@wakehealth.edu
      • Principal Investigator: Ravi Paluri, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Not yet recruiting
      • Oregon Health & Science University, Knight Cancer Institute
      • Contact: Principal Investigator; Email: kardosh@ohsu.edu
      • Principal Investigator: Adel Kardosh, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Not yet recruiting
      • Thomas Jefferson University Hospital, Sidney Kimmel Cancer Center
      • Contact: Principal Investigator
      • Contact: James.PoseyIII@jefferson.edu
      • Principal Investigator: James Posey, III, MD
  • Texas
    • Edinburg, Texas, United States, 78539
      • Not yet recruiting
      • DHR Health Advanced Care Center, DHR Oncology Institute
      • Principal Investigator: Lee Drinkard, MD
      • Contact: Prinicipal Investigator; Email: l.drinkard@dhr-rgv.com
    • San Antonio, Texas, United States, 78229
      • Not yet recruiting
      • University of Texas Health Science Center, Mays Cancer Center
      • Contact: Principal Investigator; Email: aroras@uthscsa.edu
      • Principal Investigator: Sukeshi P Arora, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Biopsy-proven HCC that is locally advanced or metastatic OR

• Patients without biopsy confirmation are also eligible if they meet one of the following criteria:

  1. Radiologic diagnosis of HCC as per the AASLD guidelines OR

  2. Liver cirrhosis AND a liver mass that shows arterial phase hyperenhancement on triphasic computed tomography (CT) or MRI, AND either:

     • Is ≥ 20 mm with either non-peripheral portal washout or an enhancing capsule OR
     • Is 10-19 mm with non-peripheral portal venous washout AND an enhancing capsule
• For Child-Pugh A participants: treatment failure (defined as documented radiological progression) and/or intolerance to at least two prior treatments with approved or experimental systemic therapies including atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib, ramucirumab, nivolumab, nivolumab plus ipilimumab, pembrolizumab or any other approved or experimental first line and/or second line therapy.
• Child-Pugh B participants are not required to have received any prior treatment.
• Measurable disease according to RECIST v 1.1.
• At least one target lesion that has not previously received any local therapy, such as surgery, radiation therapy, hepatic arterial embolization, transarterial chemoembolization (TACE), hepatic arterial infusion, radio-frequency ablation, percutaneous ethanol injection or cryoablation, unless it has subsequently progressed by 20% or more according to RECIST v 1.1 and mRECIST for HCC.

• Patients with Child-Pugh A or B (at time of enrollment) as defined by the parameters contained in the Child-Pugh Calculator. Subjects with Child-Pugh score of B8-B9 may be included if they have:

  • Albumin ≥ 2.8 mg/l AND
  • Total Bilirubin ≤ 3.0mg/l.
• ECOG performance status of 0-2.
• At least 2 weeks must have elapsed since administration of any anticancer treatment prior to initiation of protocol therapy.
• Patients must be greater than or equal to 18 years old and must be able to understand and sign an informed consent.
• Female patients of childbearing potential and their partners and male patients must agree to use adequate contraception during the period of study treatment.

Exclusion Criteria:

• Known leptomeningeal disease. (Previously treated, asymptomatic central nervous system (CNS) metastases are eligible).
• Fibrolamellar HCC or combined hepatocellular-cholangiocarcinoma (cHCC-CC).
• Prior treatment with the TheraBionic Device.
• Patients with any of the following within the 12 months prior to registration: uncontrolled/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism.
• Pregnant or breastfeeding women.
• Patients with another active malignancy within the past one year except for treated cervical cancer in situ, treated in situ carcinoma of the bladder or treated non-melanoma carcinoma of the skin, low-risk prostate cancer not requiring active treatment, treated T1/T2 glottic cancer, treated stage 0 or stage I breast cancer not requiring adjuvant therapy or treated non-invasive bladder cancer.
• Patients receiving calcium channel blockers and any agent blocking L-type of T-type Voltage Gated Calcium Channels, e.g., amlodipine, nifedipine, ethosuximide, ascorbic acid (vitamin C), etc. unless their medical treatment is modified to exclude calcium channel blockers prior to enrollment.
• Patients with curative treatment options available, including surgery or radiofrequency ablation, as assessed by their physician.
• Patients receiving other anticancer treatments.
• Patients that do not agree to be followed according to the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TheraBionic Arm - Active Arm; For subjects who are randomized to the active arm, the device will be programmed with hepatocellular carcinoma-specific modulation frequencies and will be activated for >200 one-hour treatment sessions.	Device: TheraBionic Device; Each treatment day consists of three courses of 60-minute treatments to be administered in the morning, at noon, and in the evening. Each 6-week treatment period will be considered a cycle of treatment. With the exception of the first 60-minute treatment, which will be delivered at one of the recruiting site, all other treatments will be self-administered at the patient's home.; Device: Quality of Life Assessment; Ancillary services
Placebo Comparator: Placebo Arm; For subjects randomized to the placebo arm, the device will not emit any hepatocellular carcinoma-specific modulation frequencies and will be activated for >200 one-hour treatment sessions.	Device: Quality of Life Assessment; Ancillary services; Device: Placebo Device; Each treatment day consists of three courses of 60-minute treatments to be administered in the morning, at noon, and in the evening. Each 6-week treatment period will be considered a cycle of treatment. With the exception of the first 60-minute treatment, which will be delivered at the recruiting site, all other treatments will be self-administered at the patient's home.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival assessment will be recorded in days and will represent the period starting at the date of treatment initiation and finishing at the date of patient death. Living patients at the time of analysis will have the date of last contact (consultation visit or phone contact) used to define overall survival.	Baseline to 6 months
Quality of Life Survey	Patient-reported hepatobiliary-specific disease-related symptoms will be assessed by the 18-item FACT-Hepatobiliary (Hep) subscale every cycle for the first 6 cycles then every other cycle thereafter, at the end of treatment, and at every 3 months during follow-up.	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Progression free survival (PFS) will be compared between groups using a 2-sided log rank test. Kaplan-Meier survival curves for PFS will also be generated and median progression free survival and corresponding 95% confidence intervals will be estimated for each group	Up to 2 years
Proportion of Patients With Disease Control	Proportion of patients who respond and the corresponding 95% Clopper Pearson exact confidence intervals. Patients who are removed from study before the 6-month time point will be considered to not have disease control at that time point.	At 4 months and 6 months and up to 2 years
Proportion of Participants That Are Progression Free	we will determine the proportion of patients who are progression free after 12 weeks (after 2nd 6-week visit) and compare this between groups using a Fisher's exact test. In addition, the corresponding 95% Clopper Pearson exact confidence intervals will be calculated for the 4 month and 6 month progression free survival rates.	At 12 weeks, 4 months and 6 months and up to 2 years
Incidences of Adverse Events - CTCAE version 5.0	Using Common Terminology Criteria for Adverse Events [CTCAE], version 5.0, type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities will be assessed.	Up to 28 days after study treatment administration or until death
Changes in Alfa-Fetoprotein Levels	Investigators will examine whether these is any association between the AFP levels (potential biomarker for response) and the objective response observed for each participant. Average alfa-fetoprotein levels will be examined over time, and these changes in alfa-fetoprotein rates after 6 months will be examined for each Response category (complete response/ partial response/ stable disease/ progressive disease) and tested using a 1-way ANOVA to see if the change in AFP level differs by response category.	6 months
Functional Assessment of Cancer Therapy-General (FACT-G) Item GP5	Participants will answer a single item question from the FACT-G questionnaire "I am bothered by side effects of treatment" Scoring scale of 0 (not at all) to 4 (very much) to assess for side effects to assess for patient rated treatment tolerability.	At baseline and every 6 weeks up to 6 months
Frequency of Adverse Events - PRO-CTCAE	The frequency and nature of patient-reported symptomatic adverse events will be assessed using 10 items from the PRO-CTCAE item library. PRO-CTCAE items will assess mucositis (2 items; severity, interference), dry mouth (1 item, severity), fatigue (2 items; severity, interference), decreased appetite (2 items; severity, interference), nausea (1 item, severity), and headache (2 items; severity, interference) to measure potential adverse events associated with the study intervention. Participants will select the one response that best describes their experience with a scoring scale(s) of None to Very Severe or Not at all to Very Much.	At baseline and every 8 weeks up to 6 months

Collaborators and Investigators

• Sponsor: THERABIONIC INC.
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Valerie K Pasche, MD, THERABIONIC INC.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): October 30, 2024

Study Registration Dates

• First Submitted: March 10, 2021
• First Submitted That Met QC Criteria: March 12, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 25, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Child-Pugh A and B
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: IRB00072592; R44CA256984 (U.S. NIH Grant/Contract); 20231793 (Other Identifier: WCG IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The investigators of this project will make the non-proprietary results and accomplishments of the research plan available to the research community and to the public at large by the timely release and sharing of data. As a means of sharing knowledge, the investigators supported by this grant will seek to publish the original research in primary scientific journals. The investigators will also assert copyright in scientific and technical articles based on data produced under the grant where necessary. For each publication that results from the grant-supported research, we will include an acknowledgment of NIH grant support and follow guidelines regarding free access to published materials. Information on each publication resulting from work performed under the NIH grant supported project will be included in the annual and/or final progress report submitted to the NIH awarding office.

Proprietary developments will be protected using intellectual property rights.

• IPD Sharing Time Frame: Within six months of data publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No