Meclizine for Hepatocellular Carcinoma

Completed · Phase 1

Conditions studied: Carcinoma, Hepatocellular

In brief

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.

Key facts

Study ID

NCT03253289

Run by

Tannaz Armaghnay

People needed

13

Starts

2017-10-13

Expected to finish

2023-03-28

Last updated by the study team

2024-10-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.

Where it is running

• Baylor College of Medicine -McNair Campus — Houston, Texas, United States
• Baylor College of Medicine — Houston, Texas, United States
• Baylor St. Luke's Medical Center — Houston, Texas, United States
• Ben Taub General Hospital — Houston, Texas, United States
• Harris Health System- Smith Clinic — Houston, Texas, United States

Full record on ClinicalTrials.gov

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