Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

— TheraBionics  

Official title:

A Randomized Phase II Study Of Intrabucally Administered Electromagnetic Fields Versus Placebo as Third-line Therapy For Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04526080
• Other study ID #: IRB00068320
• Secondary ID: WFBCCC 55320P30C
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 2021
• Est. completion date: November 2022

Study information

• Verified date: January 2021
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2022
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Biopsy-proven hepatocellular carcinoma that is locally advanced or metastatic

• Patients must have measurable disease.

• Failure or intolerance to prior treatments with at least two different approved or experimental systemic therapies including sorafenib, lenvatinib, regorafenib, cabozantinib, ramucirumab, nivolumab, nivolumab plus ipilumab, atezolizumab and bevacizumab, or any approved or experimental first line and/or second line therapy that did not include the TheraBionic device (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 10 weeks after the last systemic treatment

• Measurable disease according to 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, TACE, hepatic arterial infusion, radio-frequency ablation, percutaneous ethanol injection or cryoablation, unless it has subsequently progressed by 20% or more according to mRECIST for hepatocellular carcinoma.

• Patients with Child's Pugh A or B (at time of enrollment) as defined by the parameters contained in the Child Pugh Calculator.-Subjects with Child's Pugh score of B8-B9 may be included if they have: Albumin > 2.8 mg/l AND Total Bilirubin < 3.0mg/l, Performance status ECOG 0-2.

• Patient must not have curative treatment options, including surgery or radiofrequency ablation, available as assessed by their physician.

• Any extra-hepatic metastases, including treated CNS metastases but patients cannot have leptomeningeal disease.

• At least 4 weeks must have elapsed since administration of any anti-cancer treatment.

• Other anti-cancer treatments are not permitted during this study

• Patients must be more than 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 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

• Has received treatment for other carcinomas within the last three years except for cured non-melanoma skin cancer, low-risk prostate cancer, T1/T2 glottic cancer, stage 0 or stage I breast cancer, non-invasive bladder cancer, or treated in-situ cervical 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. are not allowed in the study unless their medical treatment is modified to exclude calcium channel blockers prior to enrollment.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Device:
• TheraBionic 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 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.
• Placebo Device
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.

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 months
Secondary	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.	Up to 2 years
Secondary	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	12 weeks, 4 months and 6 months
Secondary	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.	Up to 28 days after last study treatment administration
Secondary	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.	6 months
Secondary	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.	6 months