Clinical Trials /

Tazemetostat in Treating Patients With Recurrent Ovarian or Endometrial Cancer

NCT03348631

Description:

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.

Related Conditions:
  • Endometrial Endometrioid Adenocarcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
Recruiting Status:

Suspended

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tazemetostat in Treating Patients With Recurrent Ovarian or Endometrial Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-02147
  • SECONDARY ID: NCI-2017-02147
  • SECONDARY ID: NRG-GY014
  • SECONDARY ID: NRG-GY014
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03348631

Conditions

  • FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
  • FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma
  • Recurrent Endometrial Endometrioid Adenocarcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Ovarian Clear Cell Adenocarcinoma
  • Recurrent Ovarian Endometrioid Adenocarcinoma
  • Recurrent Uterine Corpus Cancer

Interventions

DrugSynonymsArms
TazemetostatE7438, EPZ-6438, EPZ6438Treatment (tazemetostat)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVE:

      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.

      SECONDARY OBJECTIVES:

      I. To examine the nature and degree of toxicity in this patient population treated with this
      regimen.

      II. To examine the progression free survival and overall survival for this patient population
      receiving tazemetostat.

      III. To evaluate BAF250a expression in patient samples as an indicator of ARID1A mutation
      status and correlation with the clinical response to study drug.

      EXPLORATORY OBJECTIVES:

      I. Translational Research Integrated Objective: Whether or not the patient has an ARID1A
      mutation. (08/13/2019) 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.

      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.

      After completion of study treatment, patients are followed up every 3 months for 2 years and
      then every 6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (tazemetostat)ExperimentalPatients receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Tazemetostat

Eligibility Criteria

        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

                    -  At least 28 days since last dose of chemotherapy prior to registration.

               -  Chemotherapy: nitrosoureas

                    -  At least 6 weeks since last dose of chemotherapy prior to registration.

               -  Chemotherapy: non-cytotoxic (e.g. small molecule inhibitor)

                    -  At least 28 days since last dose of chemotherapy prior to registration.

               -  Monoclonal antibody(ies)

                    -  At least 28 days since last dose of monoclonal antibody prior to
                       registration.

               -  Immunotherapy

                    -  At least 28 days since last dose of immunotherapy prior to registration.

               -  Radiotherapy (RT)

                    -  At least 14 days from last local site RT prior to registration.

                    -  At least 21 days from stereotactic radiosurgery prior to registration.

                    -  At least 12 weeks from craniospinal, >= 50% radiation of pelvis or total
                       body irradiation prior to registration.

                    -  Patients with central nervous system (CNS) disease should demonstrate
                       evidence of stabilization after the 28-day time point after definitive
                       treatment.

                    -  Full recovery of radiation related side effects prior to registration.

                    -  All subjects must have evidence of measurable disease outside of the
                       radiation field at the time of registration.

          -  Appropriate stage for study entry based on the following diagnostic workup:

               -  History/physical examination within 14 days prior to registration

               -  Imaging of the chest, abdomen and pelvis within 28 days prior to registration

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14
             days prior to registration

          -  Platelets >= 100,000/mcl (within 14 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)

          -  Hemoglobin (Hgb) >= 8 g/dL (within 14 days prior to 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
             registration)

          -  Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) (within 14
             days prior to registration)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within
             14 days prior to 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 registration)

          -  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 30 days 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

          -  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

        Exclusion Criteria:

          -  Prior treatment with an investigational EZH2 inhibitor

          -  Patients who are unable to swallow pills or absorb orally administered medication

          -  A prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)

          -  Abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and
             myeloproliferative neoplasms (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing
             and deoxyribonucleic acid (DNA) sequencing

          -  A prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic
             leukemia (T-ALL)

          -  Severe, active co-morbidity per the treating investigator's discretion

          -  Pregnant or lactating patients

          -  Known human immunodeficiency virus (HIV) positive patients on combination
             antiretroviral therapy are ineligible because of the potential for pharmacokinetic
             interactions with tazemetostat; in addition, treatments involved in this protocol may
             be immunosuppressive, increasing the risk of lethal infections in this patient
             population

          -  Treatment with strong inhibitors or inducers of CYP3A within 14 days of registration
             and during the study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor response
Time Frame:Up to 6 months
Safety Issue:
Description:Will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

Secondary Outcome Measures

Measure:Tumor response in patients with ARID1A mutations using tumor response
Time Frame:Up to 6 months
Safety Issue:
Description:Will be defined by RECIST v 1.1.
Measure:Incidence of adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:Will be assessed according to grade of toxicity by organ or organ system.
Measure:Progression-free survival
Time Frame:From study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Safety Issue:
Description:Will be characterized by quartiles and the median of the distribution with confidence intervals. Kaplan-Meier plots will show an estimate of the survival function for these populations.
Measure:Overall survival
Time Frame:From study entry to time of death or the date of last contact, assessed up to 5 years
Safety Issue:
Description:Will be characterized by quartiles and the median of the distribution with confidence intervals. Kaplan-Meier plots will show an estimate of the survival function for these populations.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

November 4, 2020