RECRUITING

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

Conditions

Hepatic Impairment Advanced Malignant Solid Tumor

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This main aim of this trial will be to study the blood levels (known as pharmacokinetics) of the study drug tazemetostat. The pharmacokinetics of the study drug in participants with advanced solid tumors and moderate or severe hepatic (liver) impairment will be compared with participants with advanced malignancies and normal hepatic function. An advanced malignancy is a cancer that has recurred (come back) after prior treatment or hasn't controlled with treatment. The trial will also study the safety of the study drug in participants (how well it is tolerated).

Official Title

A Phase I, Open-label Multi-dose Pharmacokinetic and Safety Study of Oral Tazemetostat in Subjects With Moderate and Severe Hepatic Impairment With Advanced Malignancies

Quick Facts

Study Start:2020-01-15

Study Completion:2025-06-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04241835

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	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.

Inclusion Criteria

Exclusion 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.

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.

Contacts and Locations

Study Contact

Ipsen Recruitment Enquiries

CONTACT

See e mail

clinical.trials@ipsen.com

Principal Investigator

Ipsen Medical Director

STUDY_DIRECTOR

Ipsen

Study Locations (Sites)

Florida Cancer Specialists & Research Institute

Lake Mary, Florida, 32746

United States

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611

United States

Hematology Oncology Consultants

Royal Oak, Michigan, 48073

United States

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, 89014

United States

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901

United States

Gabrail Cancer Center

Canton, Ohio, 44718

United States

Mary Crowley Cancer Research

Dallas, Texas, 75230

United States

Oncology Consultants - Texas Medical Center

Houston, Texas, 77030

United States

Virginia Cancer Specialists

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Epizyme, Inc.

Ipsen Medical Director, STUDY_DIRECTOR, Ipsen

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-01-15

Study Completion Date2025-06-28

Study Record Updates

Study Start Date2020-01-15

Study Completion Date2025-06-28

Terms related to this study

Additional Relevant MeSH Terms

Hepatic Impairment
Advanced Malignant Solid Tumor