Clinical Trials /

Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib

NCT04327700

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib
  • Official Title: A Phase II Study Of Intrabucally Administered Electromagnetic Fields and Regorafenib as Second-line Therapy For Patients With Advanced Hepatocellular Carcinoma.

Clinical Trial IDs

  • ORG STUDY ID: IRB00064732
  • SECONDARY ID: WFBCCC 55319
  • SECONDARY ID: P30CA012197
  • NCT ID: NCT04327700

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
RegorafenibStivargaRegorafenib and TheraBionic

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Regorafenib and TheraBionicExperimentalTheraBionic 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.
  • Regorafenib

Eligibility Criteria

        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
             {Marrero, 2018 #302}

          -  Failure to prior treatment with sorafenib or lenvatinib (defined as documented
             radiological progression according to the radiology charter).

          -  Patient must have been treated with at least one standard systemic treatment modality
             for advanced hepatocellular carcinoma such as sorafenib, lenvatanib, or other
             experimental therapies prior to study entry.

          -  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, 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 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 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 who had surgical resectin 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 of 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival
Time Frame:12 weeks
Safety Issue:
Description:Progression-free survival will be estimated along with estimates of 95% confidence intervals for the treatment group. In addition, we will determine the proportion of patients who are progression free after 12 weeks (after 2nd 6-week visit) and compare this to the proportion of patients that were described as progression free in the RESORCE trial using a Simon's two stage design.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:6 months
Safety Issue:
Description:Kaplan Meier curves for patients survival and also estimate the percent of patients who are alive at 6 months and the corresponding 95% Clopper Pearson exact confidence intervals will be calculated.
Measure:Percentage of Participants with Disease Control
Time Frame:At 4 months and at 6 months from the date of enrollment
Safety Issue:
Description: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 using a 95% Clopper Pearson exact confidence interval. 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.
Measure:Incidences of Adverse Events
Time Frame:Up to 30 days after treatment ends
Safety Issue:
Description:Type, incidence, severity of adverse events graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events will be described for each CTL type for this study using counts/percent's.
Measure:Comparison of Adverse Events (WFBCCC 55319 to RESORCE historical trial)
Time Frame:Up to 30 days after treatment ends
Safety Issue:
Description:Type, incidence, severity of adverse events graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events will be compared for each CTL type 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.
Measure:Change in Alpha-fetoprotein Levels
Time Frame:6 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Wake Forest University Health Sciences

Last Updated

March 30, 2020