Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma
Study Details
Study Description
Brief Summary
The primary goal of this study is to gather efficacy data concerning overall survival with electromagnetic fields 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Primary Objective: To estimate overall survival and quality of life.
Secondary Objectives
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To estimate progression-free survival
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To evaluate safety and tolerability in this patient population.
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To evaluate the effect on levels of alpha-fetoprotein.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TheraBionic Arm - Active Arm 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. |
Device: TheraBionic Device
Each treatment day consists of three courses of 60-minute treatments to be administered in the morning, at noon, and in the evening. Each 6-week treatment period will be considered a cycle of treatment. With the exception of the first 60-minute treatment, which will be delivered at one of the Comprehensive Cancer Centers, all other treatments will be self-administered at the patient's home.
Other: Quality of Life Assessment
Ancillary services
|
| Placebo Comparator: Placebo Arm 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. |
Drug: Placebo Device
Each treatment day consists of three courses of 60-minute treatments to be administered in the morning, at noon, and in the evening. Each 6-week treatment period will be considered a cycle of treatment. With the exception of the first 60-minute treatment, which will be delivered at one of the Comprehensive Cancer Centers, all other treatments will be self-administered at the patient's home.
Other: Quality of Life Assessment
Ancillary services
|
Outcome Measures
Primary Outcome Measures
- Overall Survival [Baseline to 6 months]
The co-primary objectives of this study are to compare overall survival (OS) and quality of life between patients receiving active vs. placebo treatment with the TheraBionic device. 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.
- Quality of Life Survey - EQ-5D-5L [Baseline to 6 months]
The primary fixed effects of interest are treatment (TheraBionic device vs Placebo) and time (baseline and every 6 week) and the time by treatment interaction. The five dimensions of the survey include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ-5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).
Secondary Outcome Measures
- Progression-Free Survival [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
- Proportion of Patients With Disease Control [At 4 months and 6 months and up to 2 years]
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.
- Proportion of Participants That Are Progression Free [At 12 weeks, 4 months and 6 months and up to 2 years]
we will determine the 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 [Up to 28 days after study treatment administration or until death]
Using Common Terminology Criteria for Adverse Events [CTCAE], version 5.0, timing, seriousness, and relatedness of adverse events and laboratory abnormalities. These adverse events will be compared for each cytotoxic T Lymphocyte 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 [6 months]
Investigators will examine whether these is any association between the AFP levels (potential biomarker for response) and the objective response observed for each participant. 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 AFP level differs by response category.
- Quality of Life Survey - FACT Hepatobiliary [At baseline and every 6 weeks up to 6 months]
The primary fixed effects of interest are treatment (TheraBionic device vs Placebo) and time (baseline and every 6 week) and the time by treatment interaction. Self-administered 45-item questionnaire on a 5 point Likert-type scale (0 not at all to 4 very much). Scoring range 0-180. Some items are reverse scored. Subscales are physical, social/family, emotional and functional well-being and hepatobiliary cancer subscale. Higher score indicates better quality of life.
Eligibility Criteria
Criteria
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:
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Radiologic diagnosis of HCC as per the AASLD guidelines OR
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Liver cirrhosis AND a liver mass that shows arterial phase hyperenhancement on triphasic computed tomography (CT) or MRI, AND either:
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Is ≥ 20 mm with either non-peripheral portal washout or an enhancing capsule OR
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Is 10-19 mm with non-peripheral portal venous washout AND an enhancing capsule
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For Child-Pugh A and B7 patients: 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.
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For patients who are Child-Pugh B8 and B9 at the time of diagnosis of locally advanced or metastatic HCC: treatment failure (defined as documented radiological progression) and/or intolerance to one immunotherapy treatment, e.g., nivolumab, atezolizumab, etc. Patients with a previously lower Child-Pugh score (A-B7) who received at least two prior lines of therapy prior to progressing to B8 or B9 disease also are eligible for the study.
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Measurable disease according to RECIST v 1.1 and mRECIST for HCC.
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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.
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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:
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Albumin ≥ 2.8 mg/l AND
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Total Bilirubin ≤ 3.0mg/l.
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ECOG performance status of 0-2.
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At least 2 weeks must have elapsed since administration of any anticancer treatment prior to initiation of protocol therapy.
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Patients must be ≥ 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:
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Known leptomeningeal disease. (Previously treated, asymptomatic central nervous system (CNS) metastases are eligible).
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Fibrolamellar HCC or combined hepatocellular-cholangiocarcinoma (cHCC-CC).
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Prior treatment with the TheraBionic Device.
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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.
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Pregnant or breastfeeding women.
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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.
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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.
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Patients with curative treatment options available, including surgery or radiofrequency ablation, as assessed by their physician.
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Patients receiving other anticancer treatments.
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Patients that do not agree to be followed up according to the study protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic College of Medicine and Science of Arizona | Phoenix | Arizona | United States | 85054 |
| 2 | Robert H. Lurie Comprehensive Cancer Center of Northwestern University | Chicago | Illinois | United States | 60611 |
| 3 | Wake Forest Baptist Comprehensive Cancer Center | Winston-Salem | North Carolina | United States | 27157 |
Sponsors and Collaborators
- Wake Forest University Health Sciences
- National Cancer Institute (NCI)
- Therabionics
Investigators
- Principal Investigator: William Blackstock, MD, Wake Forest University Health Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00072592
- WFBCCC 55121
- P30CA012197
- R44CA256984