Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma (TheraBionics)
Primary Purpose
Hepatocellular Carcinoma
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TheraBionic Device
Placebo Device
Sponsored by

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma
Eligibility Criteria
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.
Sites / Locations
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
- Memorial Sloan-Kettering Cancer Center
- Wake Forest Baptist Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TheraBionic Arm
Placebo Arm
Arm Description
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.
Placebo device that looks and sounds like the active device.
Outcomes
Primary Outcome Measures
Overall Survival
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.
Secondary Outcome Measures
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.
Proportion of Patients Progression Free After 12 weeks
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
Number of Adverse Events
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.
Changes in Alfa-Fetoprotein Levels
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.
Response Rates
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.
Full Information
NCT ID
NCT04526080
First Posted
August 21, 2020
Last Updated
February 23, 2021
Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04526080
Brief Title
Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma
Acronym
TheraBionics
Official Title
A Randomized Phase II Study Of Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Withdrawn
Why Stopped
This application needs further attention in terms of FDA approval and will be reassigned under a different trial number later.
Study Start Date
April 2021 (Anticipated)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
November 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Care ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TheraBionic Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Placebo device that looks and sounds like the active device.
Intervention Type
Device
Intervention Name(s)
TheraBionic Device
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Placebo Device
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Progression-Free Survival
Description
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.
Time Frame
Up to 2 years
Title
Proportion of Patients Progression Free After 12 weeks
Description
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
Time Frame
12 weeks, 4 months and 6 months
Title
Number of Adverse Events
Description
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.
Time Frame
Up to 28 days after last study treatment administration
Title
Changes in Alfa-Fetoprotein Levels
Description
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.
Time Frame
6 months
Title
Response Rates
Description
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.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Blackstock, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Wake Forest Baptist Comprehensive Cancer Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma
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