Tazemetostat in Treating Patients With Metastatic or Unresectable Solid Tumors or B-Cell Lymphomas With Liver Dysfunction

NCT03217253 | Withdrawn Phase 1 FDA Drug

• 4 other identifiers: NCI-2017-01231PJC-02510130UM1CA186644
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose and side effects of tazemetostat in treating patients with solid tumors or B-cell lymphomas with liver dysfunction that have spread to other places in the body or cannot be removed by surgery. Tazemetostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Ann Arbor Stage III B-Cell Non-Hodgkin Lymphoma; Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma; Metastatic Malignant Solid Neoplasm; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Unresectable Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events of tazemetostat in patients with varying degrees of hepatic dysfunction assessed using Common Terminology Criteria for Adverse Events version 5.0

  Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to study treatment.

  Up to 2 years

• Recommended phase 2 dose (RP2D) of tazemetostat in patients with varying degrees of hepatic dysfunction

  RP2D will be determined.

  Up to 2 years

Secondary Outcomes (6)

• Pharmacokinetic (PK) profiles of tazemetostat in patients with varying degrees of hepatic dysfunction

  Up to course 4 day 1 (day 85)

• Antitumor activity of tazemetostat

  Up to 2 years

• Antitumor activity of tazemetostat in population with tumors with aberrations in EZH2 or SWI/SNF complex pathways

  Up to 2 years

• Objective confirmed response

  Up to 2 years

• Duration of response

  Up to 2 years

Study Arms (1)

Treatment (tazemetostat)

EXPERIMENTAL

Patients receive tazemetostat PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Tazemetostat

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tazemetostat)

Pharmacological Study OTHER

Correlative studies

Treatment (tazemetostat)

Tazemetostat DRUG

Given PO

Also known as: E7438, EPZ-6438, EPZ6438

Treatment (tazemetostat)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically and/or cytologically confirmed solid tumors or B cell lymphoma that are metastatic or unresectable and for which standard treatment options do not exist; patients with hepatocellular carcinoma are eligible without pathological diagnosis if diagnosed on the basis of blood work and imaging
• Patients with evaluable disease will be eligible
• All patients 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 study principal investigator
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 3 months
• Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade =\< 1 (except alopecia) at the time of enrollment
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 90 g/L (9.0 g/dL)
• Creatinine within normal institutional limits OR calculated creatinine clearance \>= 60 mL/min/1.73 m\^2 (Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
• Patients with abnormal hepatic function will be eligible and will be grouped according to criteria; patients with active hemolysis should be excluded; no distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes; this data will be captured in the case report form (CRF); registration laboratory investigations will be used to assign a patient to a hepatic function group; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for 30 days after tazemetostat discontinuation
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)

You may not qualify if:

• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression as documented by computed tomography (CT) or magnetic resonance imaging (MRI) scan, analysis of cerebrospinal fluid or neurological exam; patients with primary glioblastoma multiforme are excluded
• Radiation therapy in the last 14 days; palliative radiation to a localized area without residual toxicity requires a washout of greater than 7 days
• Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders; patients on anticoagulation with low molecular weight heparin are allowed
• Known hypersensitivity to any of the components of tazemetostat
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tazemetostat
• Concurrent investigational agent or anticancer therapy
• Note: megestrol \[Megace\] if used as an appetite stimulant is allowed
• Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
• The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra \[ma huang\], ginkgo biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, or ginseng)
• 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
• Active hepatitis B virus (HBV; hepatitis B surface antigen \[HepBsAG\] positive \[+ve\] and IgM anti-hepatitis B virus core antibody \[HBc\]), or hepatitis C virus (HCV; detectable HCV ribonucleic acid \[RNA\]) infection; patients with chronic or cleared HBV and HCV infection are eligible
• Patients with known human immunodeficiency virus (HIV) infection are eligible if being treated with non-interacting antiretroviral (ARV) agents or be willing to stop ARV for the protocol
• Treatment with strong inhibitors or inducers of CYP3A are prohibited from 14 days prior to the first dose of tazemetostat to the end of the study
• Active gastrointestinal tract disease with malabsorption syndrome or unable to swallow oral medications
• Any condition or medical problem in addition to the underlying malignancy and organ dysfunction that the investigator feels would pose unacceptable risk

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Hepatocellular

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Daniel J Renouf

  University Health Network Princess Margaret Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 14, 2017
• Study Start: March 16, 2018
• Primary Completion: September 19, 2019
• Study Completion: September 19, 2019
• Last Updated: February 7, 2020

Record last verified: 2020-01

Locations

US (1)