Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Device: TheraBionic; Drug: Regorafenib

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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
• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Regorafenib and TheraBionic; 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.

Device: TheraBionic; 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.; Other Names: Amplitude-modulated electromagnetic field device; Drug: Regorafenib; 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.; Other Names: Stivarga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months
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.	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.	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.	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.	Adverse events were collected during the course of treatment with a maximum of 9 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI); THERABIONIC INC.
• Investigators: Principal Investigator: Ravi Paluri, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2021
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: March 26, 2020
• First Submitted That Met QC Criteria: March 30, 2020
• First Posted (Actual): March 31, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; regorafenib
• Other Study ID Numbers: IRB00064732; P30CA012197 (U.S. NIH Grant/Contract); WFBCCC 55319 (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: Yes
• Studies a U.S. FDA-regulated device product: Yes