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Trial record 1 of 1 for:    NRG-GY014
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Tazemetostat in Treating Patients With Recurrent Ovarian or Endometrial Cancer

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ClinicalTrials.gov Identifier: NCT03348631
Recruitment Status : Active, not recruiting
First Posted : November 21, 2017
Last Update Posted : March 30, 2023
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Recurrent Endometrial Endometrioid Adenocarcinoma Recurrent Ovarian Carcinoma Recurrent Ovarian Clear Cell Adenocarcinoma Recurrent Ovarian Endometrioid Adenocarcinoma Recurrent Uterine Corpus Cancer Procedure: Computed Tomography Procedure: Magnetic Resonance Imaging Drug: Tazemetostat Phase 2

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 29, 2019
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : January 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment (tazemetostat)
Patients receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scans and MRI on study.
 Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography

Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Drug: Tazemetostat
Given PO
Other Names:
  • E7438
  • EPZ-6438
  • EPZ6438


Outcome Measures
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Primary Outcome Measures :
  1. Tumor response [ Time Frame: Up to 6 months ]
    Will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.


Secondary Outcome Measures :
  1. Tumor response in patients with ARID1A mutations using tumor response (Removed as of version date 20-OCT-2021) [ Time Frame: Up to 6 months ]
    Will be defined by RECIST v 1.1.

  2. 6-month progression free survival (clinical benefit rate) [ Time Frame: Up to 6 months ]
  3. Incidence of adverse events [ Time Frame: Up to 5 years ]
    Will be assessed according to grade of toxicity by organ or organ system.

  4. Progression-free survival [ Time Frame: From study entry to time of progression or death, whichever occurs first, assessed up to 5 years ]
    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.

  5. Overall survival [ Time Frame: From study entry to time of death or the date of last contact, assessed up to 5 years ]
    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.


Other Outcome Measures:
  1. ARID1A mutational status [ Time Frame: Up to 6 months ]
    Associations between BAF250a and ARID1A mutations may be examined with contingency table analysis (e.g. potentially including Chi-square analyses or Spearman's correlation).

  2. BAF250a expression [ Time Frame: Up to 6 months ]
    Will be assessed by immunohistochemistry. Associations between BAF250a and ARID1A mutations may be examined with contingency table analysis (e.g. potentially including Chi-square analyses or Spearman's correlation).


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)

    • Only patients with recurrent or persistent ovarian clear cell carcinoma (OCCC) with ARID1A pathologic variant or likely pathologic variant mutations per next generation sequencing (NGS) are eligible for entry (20-OCT-2021)
    • Institutional pathology reports must be provided indicating at least 50% clear cell morphology for ovarian tumors (primary or recurrent lesions) and NGS report must be available for step 1 registration (20-OCT-2021) (09-DEC-2021)
    • All other eligibility criteria and ineligibility criteria must be met for step 2 registration (20-OCT-2021) (09-DEC-2021)
  • 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 step 2 registration.

    • Chemotherapy: nitrosoureas

      • At least 6 weeks since last dose of chemotherapy prior to step 2 registration.

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

      • At least 28 days since last dose of chemotherapy prior to step 2 registration.

    • Monoclonal antibody(ies)

      • At least 28 days since last dose of monoclonal antibody prior to step 2 registration.

    • Immunotherapy

      • At least 28 days since last dose of immunotherapy prior to step 2 registration.

    • Radiotherapy (RT)

      • At least 14 days from last local site RT prior to step 2 registration.
      • At least 21 days from stereotactic radiosurgery prior to step 2 registration.
      • At least 12 weeks from craniospinal, >= 50% radiation of pelvis or total body irradiation prior to step 2 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 step 2 registration.
      • All subjects must have evidence of measurable disease outside of the radiation field at the time of step 2 registration

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

    • History/physical examination within 14 days prior to step 2 registration
    • Imaging of the chest, abdomen and pelvis within 28 days prior to step 2 registration
  • 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:

  • Prior treatment with an investigational EZH2 inhibitor
  • 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)
  • Patients who have had therapeutic paracentesis or thoracentesis within 8 weeks prior to step 2 registration (20-OCT-2021)
  • Patients with clinical or radiographic evidence of bowel obstruction (20-OCT-2021)
  • 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 and moderate inhibitors or inducers of CYP3A within 14 days of step 2 registration and during the study treatment (20-OCT-2021)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03348631


Locations
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Sponsors and Collaborators
National Cancer Institute (NCI)
NRG Oncology
Investigators
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Principal Investigator: Ramez N Eskander NRG Oncology
More Information
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03348631    
Other Study ID Numbers: NCI-2017-02147
NCI-2017-02147 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY014 ( Other Identifier: NRG Oncology )
NRG-GY014 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: November 21, 2017    Key Record Dates
Last Update Posted: March 30, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Adenocarcinoma
Carcinoma, Endometrioid
Adenocarcinoma, Clear Cell
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
 Ovarian Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Endometrial Neoplasms
Uterine Neoplasms