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

TheraBionic

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Hepatocellular Carcinoma

Treatments: Device: Quality of Life Assessment; Device: Placebo Device; Device: TheraBionic Device

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04797884

20231793 (Other Identifier)

R44CA256984 (U.S. NIH Grant/Contract)

IRB00072592

Details and patient eligibility

About

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.

Full 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.

Enrollment: 166 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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166 participants in 2 patient groups, including a placebo group

TheraBionic Arm - Active Arm

Experimental group

Description:

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.

Treatment:

Device: TheraBionic Device

Device: Quality of Life Assessment

Placebo Arm

Placebo Comparator group

Description:

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.

Treatment:

Device: Quality of Life Assessment

Device: Placebo Device