What side effects are associated with this type of intervention?

Common treatments for Hepatocellular Carcinoma (HCC) include systemic therapies like sorafenib and lenvatinib, which can cause hypertension, diarrhea, fatigue, hand-foot skin reactions, and liver dysfunction. Immune checkpoint inhibitors may lead to immune-related adverse events such as colitis, hepatitis, pneumonitis, and endocrinopathies. Locoregional therapies like transarterial chemoembolization (TACE) can result in post-embolization syndrome, liver dysfunction, and rarely, liver abscesses. Radioembolization may cause fatigue, abdominal pain, and radiation-induced liver disease. The side effect profile of Meclizine hydrochloride as a CAR inverse agonist in HCC is not well-established but may include drowsiness and dry mouth.

What prior FDA approvals exist?

The FDA has approved several treatments for hepatocellular carcinoma (HCC), including sorafenib (Nexavar), a multitargeted tyrosine kinase inhibitor, and atezolizumab plus bevacizumab, which has shown survival benefits in advanced HCC. While Meclizine hydrochloride is being studied as a CAR inverse agonist, there are no current FDA-approved CAR inverse agonists for HCC. Other approved treatments focus on targeting molecular pathways, such as kinase inhibitors and immune checkpoint inhibitors.

What other types of research exist?

Promising novel alternatives to Meclizine hydrochloride for HCC patients include: 1) Sorafenib combined with MEK inhibitors like AZD6244, which enhances anti-tumor activity and induces apoptosis. 2) Pimozide, which promotes reversible proliferative suppression and has additive activity with sorafenib. 3) Doxorubicin drug-eluting bead transarterial chemoembolization (TACE), which has shown efficacy and safety in advanced HCC. 4) Neoadjuvant cabozantinib and nivolumab, which have converted locally advanced HCC into resectable disease with enhanced antitumor immunity.

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CAR Inverse Agonist

Meclizine for Liver Cancer (OPTIM Trial)

Phase 1

Waitlist Available

Led By Tannaz Armaghany, MD

Research Sponsored by Tannaz Armaghnay

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have imaging: CT or MRI abdomen with and without contrast confirmed or highly suspicious for Hepatocellular carcinoma

ECOG Performance status less than/equal to 2 (Karnofsky greater than 60%)

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests meclizine, an antihistamine, for treating liver cancer by stopping tumor growth and killing cancer cells. It targets liver cancer patients awaiting surgery or other treatments. Meclizine works by blocking a liver receptor involved in cell growth. Some antihistamines have shown significant antitumor activity alone or with other therapies.

Who is the study for?

This trial is for adults over 18 with confirmed Hepatocellular carcinoma who haven't had treatment for it yet. They need normal organ/marrow function, measurable disease, and a life expectancy of at least 10 weeks. Candidates must be eligible for certain cancer treatments like surgery or ablation but not liver transplant or other investigational drugs.

What is being tested?

The trial tests Meclizine, an antihistamine used against vertigo and motion sickness, as a potential therapy for liver cancer by acting as a CAR inverse agonist to block tumor growth and induce cell death. Its effects will be measured through changes in specific gene expressions.

What are the potential side effects?

Potential side effects of Meclizine may include drowsiness, dry mouth, blurred vision, constipation or urinary retention due to its antihistamine properties. The risk of severe allergic reactions is present if there's a history of allergies to similar medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My scans show signs of liver cancer.

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I can take care of myself but might not be able to do heavy physical work.

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I am eligible for surgery or other specific treatments for my condition.

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My cancer can be measured and was confirmed by a scan within the last 8 weeks.

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I have never received treatment for my liver cancer on the lesion to be biopsied.

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I am over 18 years old.

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My liver cancer diagnosis was confirmed with a biopsy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any severe illnesses or conditions that are not under control.

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I am not pregnant or breastfeeding.

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I am not currently on any other cancer treatments.

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My liver function is not classified as Child Pugh Class B or C.

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I am not eligible for a liver transplant.

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I am not taking Rifampin or St John's Wort.

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I am HIV-positive and not on antiretroviral therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment)

This trial's timeline: 3 weeks for screening, Varies for treatment, and day1 and last day of treatment(last day would be one time point between day 28 and day 35 of treatment) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Body Weight Changes

Secondary study objectives

A panel of CAR downstream target genes

Change in Ki-67 proliferation index

Change in Serum AFP

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Meclizine 100 mgExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Meclizine Oral Tablet

2017

Completed Phase 1

~20

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Hepatocellular Carcinoma (HCC) include targeted therapies, immunotherapies, and antiviral therapies. Sorafenib, a tyrosine kinase inhibitor, blocks RAF kinase and VEGFR, disrupting tumor cell proliferation and angiogenesis. Immunotherapies, such as immune checkpoint inhibitors, enhance the body's immune response against cancer cells. Antiviral therapies, particularly for HBV and HCV-related HCC, aim to reduce viral load and liver inflammation, potentially improving overall survival. Meclizine hydrochloride, studied as a CAR inverse agonist, may inhibit tumorigenesis and induce apoptosis by affecting CAR target genes. Understanding these mechanisms helps tailor treatments to disrupt cancer growth and improve patient outcomes.

Latest developments in targeted therapy for hepatocellular carcinoma.