Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma (TheraBionics)

February 23, 2021 updated by: Wake Forest University Health Sciences

A Randomized Phase II Study Of Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma

The primary goal of this study is to gather efficacy data concerning overall survival with electromagnetic field when compared to a placebo amplitude-modulated radiofrequency electromagnetic field device in subjects who have failed or are intolerant to at least two previous systemic therapies

Study Overview

Status

Withdrawn

Detailed Description

Primary Objective: To estimate overall survival.

Secondary Objectives

  • To estimate progression-free survival.
  • To evaluate safety and tolerability in this patient population.
  • To evaluate the effect on levels of alpha-fetoprotein.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Illinois
      • Chicago, Illinois, United States, 60611
        • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Biopsy-proven hepatocellular carcinoma that is locally advanced or metastatic
  • Patients must have measurable disease.
  • Failure or intolerance to prior treatments with at least two different approved or experimental systemic therapies including sorafenib, lenvatinib, regorafenib, cabozantinib, ramucirumab, nivolumab, nivolumab plus ipilumab, atezolizumab and bevacizumab, or any approved or experimental first line and/or second line therapy that did not include the TheraBionic device (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 10 weeks after the last systemic treatment
  • Measurable disease according to mRECIST for hepatocellular carcinoma.
  • At least one target lesion should not have previously received any local therapy, such as surgery, radiation therapy, hepatic arterial embolization, TACE, hepatic arterial infusion, radio-frequency ablation, percutaneous ethanol injection or cryoablation, unless it has subsequently progressed by 20% or more according to mRECIST for hepatocellular carcinoma.
  • Patients with Child's Pugh A or B (at time of enrollment) as defined by the parameters contained in the Child Pugh Calculator.-Subjects with Child's Pugh score of B8-B9 may be included if they have: Albumin > 2.8 mg/l AND Total Bilirubin < 3.0mg/l, Performance status ECOG 0-2.
  • Patient must not have curative treatment options, including surgery or radiofrequency ablation, available as assessed by their physician.
  • Any extra-hepatic metastases, including treated CNS metastases but patients cannot have leptomeningeal disease.
  • At least 4 weeks must have elapsed since administration of any anti-cancer treatment.
  • Other anti-cancer treatments are not permitted during this study
  • Patients must be more than 18 years old and must be able to understand and sign an informed consent.
  • Patient must agree to be followed up according to the study protocol.

Exclusion Criteria:

  • Known leptomeningeal disease.
  • Fibro lamellar hepatocellular carcinoma.
  • Patients with any of the following history within the 12 months prior to study drug administration: severe/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
  • Has received treatment for other carcinomas within the last three years except for cured non-melanoma skin cancer, low-risk prostate cancer, T1/T2 glottic cancer, stage 0 or stage I breast cancer, non-invasive bladder cancer, or treated in-situ cervical 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. are not allowed in the study unless their medical treatment is modified to exclude calcium channel blockers prior to enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TheraBionic Arm
Self-administered from the device that delivers low levels of radiofrequency electromagnetic fields into the body with a spoon-shaped antenna placed in the mouth.
Amplitude-modulated electromagnetic fields will be self-administered and given continuously to patients in three courses of 60-minute treatments per day, administered in the morning, at noon and in the evening at the patient's home, with the exception of the first 60-minute treatment, which will be delivered at the research site. Each 6-week treatment period will be considered a cycle of treatment. 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 more than 200 one-hour treatment sessions.
Placebo Comparator: Placebo Arm
Placebo device that looks and sounds like the active device.
Subjects who are randomized to receive placebo, will receive the same instructions and a similar device. The placebo device will look and sound the same as the active device, but will not deliver the modulation frequencies. For subjects randomized to the placebo arm, the device will not emit any hepatocellular carcinoma-modulation frequencies and will be activated for more than 200 one-hour treatment sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 6 months
Overall survival will be assessed on an intention to treat basis using a 2-sided log rank test to compare hazard rates between groups. Kaplan-Meier survival curves will also be generated and median survival and corresponding 95% confidence intervals will be estimated for each group.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: Up to 2 years
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 Progression Free After 12 weeks
Time Frame: 12 weeks, 4 months and 6 months
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
12 weeks, 4 months and 6 months
Number of Adverse Events
Time Frame: Up to 28 days after last study treatment administration
Type, incidence, severity (graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version 5.0), timing, seriousness, and relatedness of adverse events and laboratory abnormalities. adverse events will be compared for each CTL type between the two groups using the Fisher's exact test (two-sided) at level 0.05. These comparisons will be made to compare events of grade greater than or equal to 3 between each group.
Up to 28 days after last study treatment administration
Changes in Alfa-Fetoprotein Levels
Time Frame: 6 months
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 alfa-fetoprotein level differs by response category.
6 months
Response Rates
Time Frame: 6 months
Response rates we will estimate the 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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

April 1, 2021

Primary Completion (Anticipated)

November 1, 2022

Study Completion (Anticipated)

November 1, 2022

Study Registration Dates

First Submitted

August 21, 2020

First Submitted That Met QC Criteria

August 21, 2020

First Posted (Actual)

August 25, 2020

Study Record Updates

Last Update Posted (Actual)

February 26, 2021

Last Update Submitted That Met QC Criteria

February 23, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • IRB00068320
  • P30CA012197 (U.S. NIH Grant/Contract)
  • WFBCCC 55320 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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