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.
PRIMARY OBJECTIVES: I. To determine safety, tolerability and recommended phase 2 dose (RP2D) of tazemetostat in patients with varying degrees of hepatic dysfunction. SECONDARY OBJECTIVES: I. To assess the pharmacokinetics (PK) profiles of tazemetostat in patients with varying degrees of hepatic dysfunction. II. To observe preliminary antitumor activity of tazemetostat in this population, especially in tumors with aberrations in EZH2 or SWI/SNF complex pathways. OUTLINE: This is a dose escalation study. Patients receive tazemetostat orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
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.
Time frame: Up to 2 years
Recommended phase 2 dose (RP2D) of tazemetostat in patients with varying degrees of hepatic dysfunction
RP2D will be determined.
Time frame: Up to 2 years
Pharmacokinetic (PK) profiles of tazemetostat in patients with varying degrees of hepatic dysfunction
Plasma concentrations will be measured by Q2 Solutions using a validated Liquid chromatography (LC)/mass spectrometry (MS)/MS assay. Molecular and clinical predictors of clinical outcomes will be investigated using logistic regression and Cox proportional hazards models. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships. Given the small sample size, and exploratory nature of these endpoints, all pharmacodynamic analyses conducted will be considered exploratory. All analyses will be considered exploratory and inference will be performed with appropriate caution.
Time frame: Up to course 4 day 1 (day 85)
Antitumor activity of tazemetostat
Molecular and clinical predictors of clinical outcomes will be investigated using logistic regression and Cox proportional hazards models. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships. All analyses will be considered exploratory and inference will be performed with appropriate caution.
Time frame: Up to 2 years
Antitumor activity of tazemetostat in population with tumors with aberrations in EZH2 or SWI/SNF complex pathways
Molecular and clinical predictors of clinical outcomes will be investigated using logistic regression and Cox proportional hazards models. Potential predictors include clinical predictors and molecular correlates. Descriptive statistics and plotting of data will also be used to better understand potential relationships. All analyses will be considered exploratory and inference will be performed with appropriate caution.
Time frame: Up to 2 years
Objective confirmed response
Response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
Time frame: Up to 2 years
Duration of response
Response will be assessed using the RECIST criteria 1.1.
Time frame: Up to 2 years
Best response
Response will be assessed using the RECIST criteria 1.1.
Time frame: Up to 2 years
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