A Phase II Study of Tazemetostat (EPZ-6438) in Recurrent or Persistent Endometrioid or Clear Cell Carcinoma of the Ovary, and Recurrent or Persistent Endometrioid Endometrial Adenocarcinoma
A Phase II Study of Tazemetostat (EPZ-6438) in Recurrent or Persistent Endometrioid or Clear Cell Carcinoma of the Ovary, and Recurrent or Persistent Endometrioid Endometrial Adenocarcinoma
This phase II trial studies how well tazemetostat works in treating patients with ovarian or endometrial cancer that has come back (recurrent). Chemotherapy drugs, such as tazemetostat, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
PRIMARY OBJECTIVES:
I. To assess the clinical activity (overall response rate) of tazemetostat in patients with recurrent or persistent endometrioid or clear cell ovarian carcinoma, and patients with recurrent or persistent endometrioid endometrial adenocarcinoma.
II. To assess the clinical activity (response frequency) of tazemetostat in patients with recurrent or persistent clear cell ovarian carcinoma with an ARID1A mutation.
SECONDARY OBJECTIVES:
I. To examine the nature and degree of toxicity in patients with this regimen. II. To examine the progression free survival and overall survival for this patient population receiving tazemetostat.
III. To examine the 6 month clinical benefit rate in patients treated with this regimen. (20-OCT-2021) IV. To evaluate BAF250a expression in patient samples as an indicator of ARID1A mutation status and correlation with the clinical response to study drug. Note: this only applies to patients enrolled prior to the 20-OCT-2021 version date. (20-OCT-2021)
EXPLORATORY OBJECTIVES:
I. Whether or not the patient has an ARID1A mutation. (08/13/2019) Note: this only applies to patients enrolled prior to the 20-OCT-2021 version date. (20-OCT-2021) (Translational Research Integrated Objective) II. To examine the correlation between ARID1A mutation and BAF250a expression and to identify potential mutations predictive of response in patients with preserved BAF250a expression. Note: this only applies to patients enrolled prior to the 20-OCT-2021 version date. (20-OCT-2021)
OUTLINE:
Patients receive tazemetostat orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scans and magnetic resonance imaging (MRI) on study.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Inclusion Criteria:
Pathologically (histologically or cytologically) proven diagnosis of recurrent or persistent ovarian endometrioid or clear cell carcinoma, OR recurrent or persistent endometrioid endometrial adenocarcinoma; patients with recurrent endometrial cancer must have mismatch repair (MMR) immunohistochemistry completed; if they are found to be mismatch repair deficient, they should be offered treatment with immune checkpoint inhibition before consideration for treatment on trial; primary ovarian tumors must be at least 50% endometrioid or clear cell morphology, or have histologically documented recurrence with at least 50% endometrioid or clear cell morphology; institutional pathology reports must be provided indicating at least 50% endometrioid or clear cell morphology for ovarian tumors (primary or recurrent lesions)
All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
Patients must have had at least one, but no more than 3, prior cytotoxic regimens for management of primary disease; unlimited prior hormonal therapy, targeted therapy (including immunotherapy) or antiangiogenic therapy will be permitted
Patients must have completed prior therapy:
Chemotherapy: cytotoxic
Chemotherapy: nitrosoureas
Chemotherapy: non-cytotoxic (e.g. small molecule inhibitor)
Monoclonal antibody(ies)
Immunotherapy
Radiotherapy (RT)
Appropriate stage for study entry based on the following diagnostic workup:
Age >= 18
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to step 2 registration
Platelets >= 100,000/mcl (within 14 days prior to step 2 registration)
Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to step 2 registration)
Hemoglobin >= 8 g/dL (within 14 days prior to step 2 registration)
Differential with no clinically significant morphologic abnormalities on complete blood count (CBC) testing; manual differential is encouraged, if clinically indicated, and in cases where an automated differential is abnormal (within 14 days prior to step 2 registration)
Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) (within 14 days prior to step 2 registration)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to step 2 registration)
Total serum bilirubin level =< 1.5 x ULN; direct bilirubin =< ULN for subjects with total bilirubin > 1.5 x ULN (patients with isolated indirect bilirubin elevations and a history of Gilbert's syndrome are eligible) (within 14 days prior to step 2 registration)
Patients must be able to swallow and retain oral medications and not have gastrointestinal illnesses that would preclude absorption of tazemetostat as judged by the treating physician (20-OCT-2021)
Women of childbearing potential must be willing and able to use adequate contraception (hormonal and barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; theoretically, CYP3A induction with tazemetostat use may result in the loss of efficacy in hormonal contraceptives, thus a barrier method of contraception must be used in addition to hormonal contraceptives due to the potential drug-drug interaction with tazemetostat (20-OCT-2021)
The patient or a legally authorized representative must provide study-specific informed consent and authorization permitting release of personal health information prior to study entry
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (08/13/2019)
Exclusion Criteria:
Burbank, California 91505, United States
Highland Park, Illinois 60035, United States
Brighton, Michigan 48114, United States
Chelsea, Michigan 48118, United States
East China Township, Michigan 48054, United States
West Branch, Michigan 48661, United States
Ypsilanti, Michigan 48197, United States
Las Vegas, Nevada 89109, United States
Las Vegas, Nevada 89113, United States
Las Vegas, Nevada 89149, United States
Silverdale, Washington 98383, United States
Yakima, Washington 98902, United States
Summit, Wisconsin 53066, United States