Brief Summary

Meclizine hydrochloride is an antihistamine widely used for treatment of vertigo and motion sickness. In HCC it has been used for anti-emetic effects, but it is used here as a CAR (constitutive androstane receptor) inverse agonist. The hypothesis of this study is that Meclizine, CAR inverse agonist, will have beneficial therapeutic effect in patients with hepatocellular carcinoma who are candidates for surgical resection, ablation, TACE, Y90 or systemic therapy by blocking tumorigenesis and inducing apoptosis. The effects of Meclizine will be analyzed by measuring messenger RNA level of CAR target genes CYP2B6, c-Myc and FoxM1, the downstream effectors of CAR, by real time quantitative PCR.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_1

Timeline

Completed

Started Oct 2017

Longer than P75 for phase_1

Geographic Reach

1 country

5 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.5 years study duration

First Submitted

Initial submission to the registry

May 19, 2017

Completed

3 months until next milestone

First Posted

Study publicly available on registry

August 17, 2017

Completed

2 months until next milestone

Study Start

First participant enrolled

October 13, 2017

Completed

5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 28, 2023

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 28, 2023

Completed

Last Updated

October 2, 2024

Status Verified

September 1, 2024

Enrollment Period

5.5 years

First QC Date

May 19, 2017

Last Update Submit

October 1, 2024

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular carcinoma, HCC, Liver cancer

Outcome Measures

Primary Outcomes (1)

Change in mRNA levels
Quantitative real time PCR(qPCR) can give change in expression level compared to control Delta CT value. Downstream target genes of CAR (CYP2b6,c-Myc, and FoxM) will be measured by qPCR in the pre and post treatment Hepatocellular cancer tissue specimens. The qPCR machine measures the intensity of fluorescence emitted by the probe at each cycle. The Ct measure is a determined PCR cycle and represents the basic result of a qPCR experience. The Ct is the value where the PCR curve crosses the threshold.
day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)

Secondary Outcomes (6)

Change in Ki-67 proliferation index
day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)
change in apoptosis by TUNEL assay
day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)
Tumor response
day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)
Change in Serum AFP
day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)
Change in growth differentiation factor (GDF-15)
day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)
+1 more secondary outcomes

Study Arms (1)

Meclizine 100 mg

EXPERIMENTAL

Meclizine 50 mg will be taken by the patient orally twice daily for a total of 28 days(up to 35 days).

Drug: Meclizine Oral Tablet

Interventions

Meclizine Oral TabletDRUG

All subjects will receive 50 mg of meclizine taken orally, twice a day (daily dose 100 mg) for 28 (up to 35) days.

Meclizine 100 mg

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patients must have imaging: CT or MRI abdomen with and without contrast confirmed or highly suspicious for Hepatocellular carcinoma. Patients must have a liver biopsy confirmed for Hepatocellular carcinoma.
Patients must have measurable disease, defined as tumor mass which is \>10 mm with spiral CT scan or MRI. Baseline imaging scan must be within 8 weeks of registration.
Patients must have no prior history of treatment for HCC (treatment naïve) on the lesion that is being targeted for biopsy. New HCC lesions can arise in the liver of patients despite local therapy of other areas of the liver due to consistent underlying risk factors such as cirrhosis, and chronic hepatitis B or C infection. Patients with prior local liver directed therapy such as TACE, Ablation, Y-90 or hepatectomy surgery for HCC are eligible if they have developed a new untreated lesion in the liver which can be targeted for a biopsy for this study. There is no required time frame or washout period from when a lesion has been locally treated to the time when a new lesion is found and targeted for biopsy for this trial. Patients who have had prior systemic therapy of any kind are not eligible.
Patients must be greater than 18 years of age.
ECOG Performance status less than/equal to 2 (Karnofsky greater than 60%).
Patients must have normal organ and marrow function as defined below, within 21 days of registration: Leukocytes greater than 3,000/mcL; ANC greater than 1,500/mcL; Platelets greater than 50,000/mcL; Hemoglobin greater than/equal to 8 g/dL; ALT(SGPT) less than/equal to 5X IULN and AST (SGOT) less than/equal to 5X IULN; Creatinine less than/equal to 2X IULN or Creatinine clearance greater than 60 mL/min for patients with creatinine levels greater than IULN; Child Pugh Class A (5-6 points) or B (7 points); INR less than/equal to 2.3; Albumin greater than 2.8 g/dL; Total bilirubin less than/equal to 3X IULN.
Patients must be candidate for surgical resection, ablation, TACE, Y90 or systemic therapy.
Patients should have life expectancy greater than/equal to 10 weeks.
Willingness to Use Contraception: The effects of Meclizine on the developing human fetus at the recommended therapeutic dose are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment with meclizine. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. If a male participant impregnates his partner he should inform his treating physician immediately.
Patients must be informed of the investigational nature of this study, and must sign and give written informed consent in accordance with institutional and federal guidelines.

You may not qualify if:

Patients may not be receiving any other concurrent anti-cancer therapy.
Patients may not be receiving any other concurrent investigational agents.
Patients taking medications with a narrow therapeutic index including warfarin, digoxin, phenobarbital, carbamazepine, and cyclosporine are not excluded but should be monitored carefully.
Patients must not be taking Rifampin or St John's Wort.
Patient must not have a history of allergic reactions like anaphylaxis attributed to compounds of similar chemical or biologic composition to Meclizine such as antihistamine drugs.
Patient must not be a candidate for liver transplant.
Child Pugh Class B (8,9) and Class C are excluded
Antiviral therapy for HCV and HBV is allowed, but patient should not be on interferon.
HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with meclizine.
Patient must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction or cerebrovascular accident within 6 months prior to registration, cardiac arrhythmia, glaucoma, asthma or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because meclizine is a Class B agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with meclizine, breastfeeding should be discontinued if the mother is treated with meclizine.

Contact the study team to confirm eligibility.