What side effects are associated with this type of intervention?

Common treatments for liver disease include medications like ursodeoxycholic acid (UDCA), bezafibrate, and tolvaptan. UDCA is generally well-tolerated but can cause diarrhea and weight gain. Bezafibrate may lead to gastrointestinal issues, elevated liver enzymes, and muscle pain. Tolvaptan, used for hepatic edema, can cause thirst, dry mouth, and increased urination. While specific side effects of Tazemetostat (an EZH2 inhibitor) are not detailed, similar cancer treatments often have side effects like nausea, fatigue, and liver enzyme abnormalities.

What prior FDA approvals exist?

The FDA has approved several treatments for liver diseases, including ursodeoxycholic acid (UDCA) for primary biliary cholangitis (PBC) and obeticholic acid for patients with an inadequate response to UDCA. For hepatocellular carcinoma (HCC), treatments like lenvatinib and transarterial chemoembolization (TACE) are used. While Tazemetostat, an EZH2 inhibitor, is being studied for its pharmacokinetics and safety in patients with advanced cancer and liver impairment, it represents a novel approach compared to the existing therapies for liver diseases.

What other types of research exist?

Promising novel alternatives to Tazemetostat for liver disease patients include: 1) Ezetimibe, which has shown potential in attenuating steatohepatitis and improving liver fibrosis in preclinical models. 2) Thyroid hormone receptor (THR) agonists, currently in phase 3 clinical trials for NAFLD/NASH treatment. 3) Combination therapies involving transarterial chemoembolization (TACE) with agents like sorafenib or lenvatinib, which have shown efficacy in treating hepatocellular carcinoma.

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Histone Methyltransferase Inhibitor

Tazemetostat for Advanced Cancer with Liver Impairment

Phase 1

Recruiting

Research Sponsored by Epizyme, Inc.

Eligibility Criteria Checklist

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

Must have

Able to swallow and retain orally-administered medication and without clinically significant gastrointestinal abnormalities that could alter absorption such as malabsorption syndrome or major resection of the stomach or bowels

Has the ability to understand informed consent and provided signed written informed consent

Must not have

Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's Wort)

Acute damage of the liver with Grade 4 AST/ALT values at screening or admission

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests tazemetostat, an oral medication, in patients with advanced solid tumors and different liver functions. It aims to understand how the drug behaves in the body and its safety. Researchers will measure drug levels in the blood and monitor for side effects. Tazemetostat is approved by the FDA for certain types of cancer.

Who is the study for?

Adults with advanced cancer and liver impairment or normal liver function can join this trial. They should be able to understand the study, have a life expectancy over 3 months, and not have had recent treatments that could affect results. Participants must use effective contraception if of childbearing potential and cannot have certain blood disorders or severe allergies to tazemetostat components.

What is being tested?

The trial is testing how different levels of liver function affect the blood levels and safety of Tazemetostat in patients with advanced solid tumors. It compares those with moderate/severe liver problems to those with normal liver function, focusing on how well they tolerate the drug.

What are the potential side effects?

Tazemetostat may cause fatigue, digestive issues, changes in blood counts which could lead to bleeding or infection risks, and possibly allergic reactions for those sensitive to its ingredients.

Eligibility Criteria

Inclusion Criteria

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

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I can take pills and don't have major stomach or bowel issues affecting drug absorption.

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I understand the study details and have signed the consent form.

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I am a male who will use contraception or practice abstinence during and for 3 months after the study.

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My cancer has advanced after treatment and no standard therapies are available.

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My blood, bone marrow, and kidney functions are all within normal ranges.

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My side effects from previous treatments are mild or stable.

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I can take care of myself and am up and about more than half of my waking hours.

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I am 18 years old or older.

Exclusion Criteria

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

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I am not taking strong CYP3A4 drugs or St. John's Wort.

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My liver tests are extremely high.

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I have severe blood cell count issues or a history of blood cancer.

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I have previously been treated with tazemetostat or similar medications.

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I do not have active brain or spinal cord issues from cancer.

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I do not have any severe illnesses that could interfere with the study.

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I have severe ascites needing drainage and albumin.

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I do not have an active hepatitis B, C, or HTLV-1 infection.

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My tests show genetic changes linked to certain blood disorders.

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I have a history of T-cell lymphoblastic lymphoma/leukemia.

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I have had a liver transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 1 year for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-8: area under the plasma concentration-time curve from time 0 to 8 hours post dose

To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-t: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration

To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-∞: area under the plasma concentration-time curve from time 0 extrapolated to infinity

+4 more

Secondary study objectives

To evaluate the number of participants with adverse events (AEs) as assessed by CTCAE v5.0

Side effects data

From 2021 Phase 2 trial • 20 Patients • NCT03456726

53%

Dysgeusia

41%

Nasopharyngitis

29%

Blood creatine phosphokinase increased

29%

Upper respiratory tract infection

29%

Lymphopenia

29%

Constipation

29%

Stomatitis

24%

Rash

18%

Weight decreased

18%

Blood creatinine increased

18%

Thrombocytopenia

18%

Neutropenia

18%

Nausea

12%

Influenza

12%

Amylase increased

12%

Herpes simplex

12%

Malaise

12%

Pneumonia

12%

Urinary tract infection

12%

Hypertriglyceridaemia

12%

Anaemia

12%

Hypophosphataemia

12%

Alopecia

12%

Eczema

Upper respiratory tract inflammation

Traumatic fracture

Aspartate aminotransferase increased

Blood zinc decreased

Haematuria

Electrocardiogram QT prolonged

Skin exfoliation

Oedema peripheral

Hypoalbuminaemia

Fatigue

Gastroenteritis

Impetigo

Blood pressure decreased

Visual field defect

Osteonecrosis of jaw

Hypogammaglobulinaemia

Rash maculo-papular

Phlebitis

Nail disorder

Pyrexia

Myalgia

Gamma-glutamyltransferase increased

Insomnia

Traumatic intracranial haemorrhage

Hypertonic bladder

Musculoskeletal chest pain

Gastric cancer

Non-small cell lung cancer

Haematochezia

Tooth disorder

Bronchitis

Abdominal pain

Large intestine polyp

Pneumocystis jirovecii pneumonia

Alanine aminotransferase increased

Immature granulocyte count increased

Cataract

Mechanical ileus

Atypical pneumonia

Periodontitis

Pneumonia aspiration

Leukopenia

Pericardial effusion

Conjunctival haemorrhage

Visual impairment

Epigastric discomfort

Oral herpes

Paronychia

Fall

Postoperative delirium

Procedural pain

Skin laceration

Tooth fracture

Hyperglycaemia

Hyperkalaemia

Hyperuricaemia

Pain in extremity

Tendon disorder

Myelodysplastic syndrome

Muscle spasticity

Peripheral motor neuropathy

Sciatica

Syncope

Asthma

Dysphonia

Erythema multiforme

Keloid scar

100%

80%

60%

40%

20%

Study treatment Arm

Participants With Follicular Lymphoma

Participants With Diffuse Large B-cell Lymphoma

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: Open label TazemetostatExperimental Treatment1 Intervention

Part 1: Participants will receive a single oral 800 mg dose on day 1, and twice daily from day 5 to day 14. Participants will return to the clinical study unit on an out-patient basis from day 15 to day 18. A single oral 800 mg dose of tazemetostat will be administered on day 15. Part 2: Will begin on day 19 and participants continuing treatment in Part 2 will receive tazemetostat (oral 800 mg dose) tablets to be taken twice daily in repeated 28-day cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tazemetostat

2016

Completed Phase 2

~1050

0 / 19Eligibility 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 liver disease include ursodeoxycholic acid (UDCA), bezafibrate, and obeticholic acid. UDCA works by reducing the production of toxic bile acids and improving bile flow, which helps protect liver cells. Bezafibrate, a fibrate, activates peroxisome proliferator-activated receptors (PPARs) to reduce inflammation and improve lipid metabolism. Obeticholic acid, a farnesoid X receptor (FXR) agonist, decreases bile acid synthesis and increases bile flow. Tazemetostat, an EZH2 inhibitor, targets epigenetic regulation to inhibit cancer cell growth. Understanding these mechanisms is crucial for liver disease patients as it helps tailor treatments to specific disease processes, potentially improving outcomes and minimizing side effects.

Factors predictive of the efficacy of bezafibrate therapy in patients with primary sclerosing cholangitis.Biochemical responses to bezafibrate improve long-term outcome in asymptomatic patients with primary biliary cirrhosis refractory to UDCA.