A Study to Compare the Blood Levels and Safety of Tazemetostat in Participants With Advanced Cancer and Moderate/Severe Liver Impairment to Participants With Advanced Cancer and Normal Liver Function

Launched by EPIZYME, INC. · Jan 22, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a medication called tazemetostat, which is being tested to see how it behaves in the body of patients with advanced cancer who also have liver problems, compared to those with normal liver function. The main goals are to understand how much of the drug gets into the bloodstream (this is called pharmacokinetics) and to check how safe the drug is for these patients. It is important for patients with advanced cancer, especially those whose cancer has not responded to previous treatments, to know how this drug may affect them differently depending on their liver health.

To participate in this trial, patients must be at least 18 years old and have advanced cancer that has either come back after treatment or hasn’t responded to treatment. They should also have a life expectancy of more than three months and be able to tolerate oral medications. Participants will undergo regular check-ups to monitor their health and how well they respond to the drug. It's essential for potential participants to discuss any questions or concerns with their healthcare provider, especially regarding their liver health and other medical conditions, to ensure they meet the trial's requirements.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Male or female ≥ 18 years age at the time of consent.
• • 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• • 3. Has the ability to understand informed consent and provided signed written informed consent.
• • 4. Life expectancy of \> 3 months.
• • 5. Histologically and/or cytologically confirmed advanced metastatic or unresectable solid tumors has progressed after treatment for which there are no standard therapies available OR histologically and/or cytologically confirmed hematological malignancies that have relapsed, or refractory disease following at least 2 standard lines of systemic therapy for which there are no standard therapies available.
• • 6. Must have evaluable or measurable disease.
• • 7. Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤ Grade 1 per NCI CTCAE, Version 5.0 or are clinically stable and not clinically significant, at time of consent.
• • 8. All subjects must have completed any prior chemotherapy, targeted therapy and major surgery, ≥ 28 days before study entry. For daily or weekly chemotherapy without the potential for delayed toxicity, a washout period of 14 days may be acceptable, and questions related to this can be discussed with the Medical Monitor.
• • 9. Has adequate hematologic (bone marrow \[BM\] and coagulation factors), and renal function.
• • 10. 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.
• • 11. Subjects with abnormal hepatic function will be eligible and will be grouped according to established criteria. Subjects with active hemolysis will be excluded.
• • 12. Manual differential with no significant morphologic abnormalities on complete blood count (CBC) testing.
• • 13. Male subjects must have had a successful vasectomy OR must either practice complete abstinence or agree to use a latex or synthetic condom during sexual contact with a female of childbearing potential from the first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.
• • 14. Females of childbearing potential must have a negative serum pregnancy test at screening and within 24 hours prior to the first dose of study drug. All females will be considered of childbearing potential unless they are naturally postmenopausal or have been sterilized.
• • 15. Females of childbearing potential (FCBP) must either practice complete abstinence or agree to use a highly effective method of contraception beginning at least 28 days prior to the first dose of study drug, during study treatment (including during dose interruptions), and for 6 months after study drug discontinuation.
• • 16. Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec.
• • 17. Subjects with diagnosed human immunodeficiency virus (HIV) are eligible to participate in the study if they meet established criteria.
• Exclusion Criteria:
• • 1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
• • 2. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam. Subjects with primary glioblastoma multiforme are excluded.
• • 3. Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders. Subjects on anticoagulation with low molecular weight heparin are allowed.
• • 4. Known hypersensitivity to any of the components of tazemetostat.
• • 5. Concurrent investigational agent or anticancer therapy. NOTE: Megestrol (Megace) if used as an appetite stimulant is allowed.
• • 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
• • 7. Have a known active infection with hepatitis B virus (HBV, as measured by positive hepatitis B surface antigen, hepatitis C virus (HCV, as measured by positive hepatitis C antibody), OR human T-cell lymphotropic virus 1.
• • 8. Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's Wort).
• • 9. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from 24 hours prior to the first dose of study drug until the last dose of study drug.
• • 10. Any condition or medical problem in addition to the underlying malignancy and organ dysfunction that the Investigator feels would pose unacceptable risk.
• • 11. Has thrombocytopenia, neutropenia, or anemia of grade ≥3 (per CTCAE 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
• • 12. Has abnormalities known to be associated with MDS and myeloproliferative neoplasms (MPN) observed in cytogenetic testing and DNA sequencing.
• • 13. Has a prior history of T-LBL/T-ALL.
• • 14. Ingestion of alcohol and smoking is not permitted any time during the study.
• • 15. History of drug abuse (including alcohol) within the last 6 months prior to screening.
• • 16. Severe hepatic encephalopathy (Grade \>2) or degree of CNS impairment which the Investigator considers sufficiently serious to interfere with the informed consent, the conduct, the completion, or the results of this trial, or constitutes an unacceptable risk to the subject.
• • 17. History of liver transplantation.
• • 18. Advanced ascites or ascites that require drainage and albumin supplementation, as judged by the Investigator.
• • 19. Acute damage of the liver with Grade 4 AST/ALT values at screening or admission.