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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
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.
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.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
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.
Time frame: 6 months
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.
Time frame: Up to 2 years
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
Time frame: 12 weeks, 4 months and 6 months
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.
Time frame: Up to 28 days after last study treatment administration
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.
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Time frame: 6 months
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.
Time frame: 6 months