Hepatocellular CarcinomaPhase 2NCT04327700
Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib
A Phase 2 study testing TheraBionic and Regorafenib in people with Hepatocellular Carcinoma, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The primary goal of this study is to gather efficacy data concerning the progression-free survival rate with electromagnetic fields plus Regorafenib when compared to historical data with Regorafenib alone as a second-line therapy in patients with advanced hepatocellular carcinoma who have received any first line… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- TheraBionic and Regorafenib
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jan 2021to 31 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy-proven hepatocellular carcinoma is locally advanced or metastatic. OR
- Patients without biopsy confirmation are also eligible if they meet the following:
- Radiologic diagnosis of hepatocellular carcinoma as per the American Association for the Study of Liver Diseases (AASLD) guidelines:
- liver cirrhosis AND
- a liver mass confirmed by blinded independent central review that shows arterial phase hyperenhancement on triphasic CT or MRI, AND EITHER:
- Is ≥20 mm with either non-peripheral portal washout or an enhancing capsule
Show all 19Show fewer
- OR is 10-19 mm with non-peripheral portal venous washout AND an enhancing capsule.
- Patient must have been treated with at least one standard systemic treatment modality for advanced hepatocellular carcinoma such as sorafenib, lenvatanib, atezolizumab plus bevacizumab, or another approved or experimental systemic therapy prior to study entry.
- Measurable disease according to RECIST version 1.1 and 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, 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 version 1.1 and mRECIST for hepatocellular carcinoma.
- Patients with Child's Pugh A (at time of enrollment), with compensated cirrhosis, as defined by the parameters contained in the Child Pugh Calculator found in Appendix E.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
- Absence of medical or psychiatric contraindication which, in the opinion of the treating Investigator, would make the patient's participation in this trial inappropriate.
- Patient must not have curative treatment options, including surgery or radiofrequency ablation, available.
- Any extra-hepatic metastases, including treated central nervous system metastases but patients cannot have leptomeningeal disease.
- At least 2 weeks must have elapsed since administration of any anti-cancer treatment.
- Other anti-cancer treatments are not permitted during this study, including alternative medicine and herbal therapies.
- Patients must be 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.
Who cannot join
- Known leptomeningeal disease.
- Fibro lamellar hepatocellular carcinoma.
- Patients who had surgical resection of the disease and who do not have measurable disease.
- 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.
- Patients diagnosed with another type of cancer (excluding basal cell carcinoma) whose cancer diagnosed previously is not in remission.
- Patients receiving calcium channel blockers and any agent blocking L-type or T-type Voltage Gated Calcium Channels, e.g. amlodipoine, nifedipine, ethosuximide, etc. are not allowed in the study unless their medical treatment is modified to exclude calcium channel blockers prior to enrollment.
- Patients allergic or intolerant to Sorafenib.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase II Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib as Second-line Therapy For Patients With Advanced Hepatocellular Carcinoma.
The primary goal of this study is to gather efficacy data concerning the progression-free survival rate with electromagnetic fields plus Regorafenib when compared to historical data with Regorafenib alone as a second-line therapy in patients with advanced hepatocellular carcinoma who have received any first line systemic therapy either standard of care Sorafenib or Lenvatinib or any experimental therapy. Patients who have received any treatment that includes either electromagnetic fields or Regorafenib will be excluded.
Read the detailed description
Primary Objective: To estimate progression-free survival rates.
Secondary Objectives
- To obtain information concerning the feasibility of administration of the proposed treatment, including patient participation in trials using the proposed treatment.
- To evaluate safety and tolerability in this patient population.
- To evaluate the effect on levels of alpha-fetoprotein.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- TheraBionic, Regorafenib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TheraBionicDevice
Also called Amplitude-modulated electromagnetic field device
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 4 week treatment period will be considered a cycle of treatment.
RegorafenibDrug
Also called Stivarga
Patients will receive 160 mg regorafenib (four 40 mg tablets) orally once daily for the first 3 weeks of each 4-week cycle per approved prescribing information.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib and TheraBionic | Experimental | TheraBionic is a device that consists of battery-driven radiofrequency electromagnetic field generator. The metal mouth spoon antenna is placed on the anterior part of the tongue during treatment.
Regorafenib is a 40 mg tablet administered orally. Receives: Device: TheraBionic; Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival
Progression-free survival (PFS) at 12 weeks after study enrollment. PFS assessment will be recorded in days and will represent the period starting at the date of enrollment and finishing at the later of the date of documentation of radiologic tumor progression, date of last follow-up on study treatment or death, whichever comes first. Patients who initiate post-study anti-tumor therapy prior to radiologic progression will be censored for PFS at that date. PFS is defined as at least a 20% increase in the sum of the longest diameters of target lesions compared to the smallest sum recorded (nadir), plus an absolute increase of at least 5 mm.
Measured: 12 weeks
Secondary outcomes (5)
Overall Survival
Overall Survival (OS) at 12 weeks. OS assessment will be recorded in days and will represent the period starting at the date of enrollment and finishing at the later of the date of last follow-up on study or death, whichever comes first.
Measured: 12 weeks
Percentage of Participants With Disease Control
Disease control is defined as the percentage of participants alive and have documented response status of complete response, partial response or stable disease according to the modified RECIST (mRECIST) for hepatocellular carcinoma. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of longest diameters of target lesions, without evidence of disease progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Measured: At 12 weeks
Adverse Events by Body System
Type and incidence adverse events grade 2 or higher, graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events will be described for this study using counts/percents.
Measured: Up to 30 days after study completion, up to 9 months
Number of Participants With Grade 3+ Adverse Events - Comparison of Adverse Events (WFBCCC 55319 to RESORCE Historical Trial)
Any grade 3+ adverse event graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Adverse events will be compared for the treatment group (WFBCCC 55319 study) and historical control (from the RESORCE trial), 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.
Measured: Adverse events were collected during the course of treatment with a maximum of 9 months
Change in Alpha-fetoprotein Levels
Average alpha-fetoprotein level 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 alpha-fetoprotein level differs by response category.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2020
- Study start26 Jan 2021
- Primary completion31 May 2024
- Study completion31 May 2024
Why it stopped: Slow accruals
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), THERABIONIC INC.
- Responsible party
- Sponsor
- Investigators
- Ravi Paluri, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04327700
- Sponsor's protocol ID
- IRB00064732
- Other IDs
- WFBCCC 55319, P30CA012197
- Status last verified
- Mar 2026
- First submitted
- 26 Mar 2020
- Last updated
- 5 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib as Second-line Therapy For Patients With Advanced Hepatocellular Carcinoma.
- ClinicalTrials.gov ID
- NCT04327700
- Acronym / sponsor ID
- IRB00064732
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accruals
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), THERABIONIC INC.
- Study start
- 26 Jan 2021 (actual)
- Primary completion
- 31 May 2024 (actual)
- Study completion
- 31 May 2024 (actual)
- First posted
- 31 Mar 2020 (actual)
- Results
- Posted 5 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary goal of this study is to gather efficacy data concerning the progression-free survival rate with electromagnetic fields plus Regorafenib when compared to historical data with Regorafenib alone as a second-line therapy in patients with advanced hepatocellular carcinoma who have received any first line systemic therapy either standard of care Sorafenib or Lenvatinib or any experimental therapy. Patients who have received any treatment that includes either electromagnetic fields or Regorafenib will be excluded.
Detailed description
Primary Objective: To estimate progression-free survival rates.
Secondary Objectives
- To obtain information concerning the feasibility of administration of the proposed treatment, including patient participation in trials using the proposed treatment.
- To evaluate safety and tolerability in this patient population.
- To evaluate the effect on levels of alpha-fetoprotein.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib and TheraBionic | Experimental | Device: TheraBionic, Drug: RegorafenibTheraBionic is a device that consists of battery-driven radiofrequency electromagnetic field generator. The metal mouth spoon antenna is placed on the anterior part of the tongue during treatment. Regorafenib is a 40 mg tablet administered orally. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Biopsy-proven hepatocellular carcinoma is locally advanced or metastatic. OR
- Patients without biopsy confirmation are also eligible if they meet the following:
- Radiologic diagnosis of hepatocellular carcinoma as per the American Association for the Study of Liver Diseases (AASLD) guidelines:
- liver cirrhosis AND
- a liver mass confirmed by blinded independent central review that shows arterial phase hyperenhancement on triphasic CT or MRI, AND EITHER:
Key exclusion criteria (8 listed)
- Known leptomeningeal disease.
- Fibro lamellar hepatocellular carcinoma.
- Patients who had surgical resection of the disease and who do not have measurable disease.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TheraBionicAlso: Amplitude-modulated electromagnetic field deviceAmplitude-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 4 week treatment period will be considered a cycle of treatment. | Device | Regorafenib and TheraBionic |
| RegorafenibAlso: StivargaPatients will receive 160 mg regorafenib (four 40 mg tablets) orally once daily for the first 3 weeks of each 4-week cycle per approved prescribing information. | Drug | Regorafenib and TheraBionic |
Primary outcome
Progression-Free Survival
Time frame: 12 weeks
Progression-free survival (PFS) at 12 weeks after study enrollment. PFS assessment will be recorded in days and will represent the period starting at the date of enrollment and finishing at the later of the date of documentation of radiologic tumor progression, date of last follow-up on study treatment or death, whichever comes first. Patients who initiate post-study anti-tumor therapy prior to radiologic progression will be censored for PFS at that date. PFS is defined as at least a 20% increase in the sum of the longest diameters of target lesions compared to the smallest sum recorded (nadir), plus an absolute increase of at least 5 mm.
5 secondary outcomes
Overall Survival
Time frame: 12 weeks
Percentage of Participants With Disease Control
Time frame: At 12 weeks
Adverse Events by Body System
Time frame: Up to 30 days after study completion, up to 9 months
Number of Participants With Grade 3+ Adverse Events - Comparison of Adverse Events (WFBCCC 55319 to RESORCE Historical Trial)
Time frame: Adverse events were collected during the course of treatment with a maximum of 9 months
Change in Alpha-fetoprotein Levels
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi Paluri, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TheraBionic and Regorafenib in people with Hepatocellular Carcinoma, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.