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Tazemetostat in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Endometrial Cancer

This study is not yet open for participant recruitment.
Verified November 2017 by National Cancer Institute (NCI)
Sponsor:
ClinicalTrials.gov Identifier:
NCT03348631
First Posted: November 21, 2017
Last Update Posted: November 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This phase II trial studies how well tazemetostat works in treating patients with ovarian, primary peritoneal, or endometrial cancer that has come back. Drugs used in chemotherapy, 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 Intervention Phase
Grade 1 Endometrial Endometrioid Adenocarcinoma Grade 2 Endometrial Endometrioid Adenocarcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Recurrent Uterine Corpus Carcinoma Other: Laboratory Biomarker Analysis Drug: Tazemetostat Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Tazemetostat (EPZ-6438) in Recurrent Endometrioid/Clear Cell Carcinoma of the Ovary or Peritoneum, and Recurrent Low Grade Endometrioid Endometrial Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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

Secondary Outcome Measures:
  • Incidence of adverse events according to grade of toxicity by organ or organ system [ Time Frame: Up to 5 years ]
  • 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.

  • 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.

  • Tumor response in patients with ARID1A mutations using tumor response as defined by RECIST v 1.1 [ Time Frame: Up to 6 months ]

Estimated Enrollment: 43
Anticipated Study Start Date: June 22, 2018
Estimated Study Completion Date: January 31, 2025
Estimated Primary Completion Date: January 31, 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tazemetostat)
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
Correlative studies
Drug: Tazemetostat
Given PO
Other Names:
  • E7438
  • EPZ-6438
  • EPZ6438

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 or primary peritoneal cancer, and low grade 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.

TERTIARY OBJECTIVES:

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

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. Courses 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of recurrent/persistent ovarian, or peritoneal endometrioid/clear cell carcinoma, OR recurrent/persistent low grade (grade 1 or 2) endometrioid endometrial adenocarcinoma; primary ovarian tumors must be at least 50% endometrioid/clear cell morphology, or have histologically documented recurrence with at least 50% endometrioid/clear cell morphology; appropriate tissue sections must be available for histologic evaluation for central pathology review by National Research Group (NRG) Oncology
  • 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 prior platinum-based chemotherapeutic regimen for management of primary disease; unlimited prior hormonal therapy, targeted therapy or antiangiogenic therapy will be permitted
  • Patients must be 7 days to 6 weeks out from prior therapy:

    • Chemotherapy cytotoxic: At least 21 days since last dose of chemotherapy prior to first dose of tazemetostat
    • Chemotherapy nitrosoureas: At least 6 weeks since last dose of chemotherapy prior to first dose of tazemetostat
    • Chemotherapy non-cytotoxic (e.g. small molecule inhibitor): At least 7 days or five half-lives, whichever is shorter, since last dose of chemotherapy prior to first dose of tazemetostat
    • Monoclonal antibody(ies): At least 28 days since last dose of chemotherapy prior to first dose of tazemetostat
    • Immunotherapy: At least 21 days since last dose of chemotherapy prior to first dose of tazemetostat
    • Radiotherapy (RT): At least 28 days from last local site RT prior to first dose of tazemetostat
    • At least 21 days from stereotactic radiosurgery prior to first dose of tazemetostat
    • At least 28 days from craniospinal, > 50% radiation of pelvis or total body irradiation prior to first dose of tazemetostat
  • Appropriate stage for study entry based on the following diagnostic workup:

    • History/physical examination within 28 days prior to registration
    • Imaging of the chest, abdomen and pelvis within 30 days prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 28 days prior to registration
  • Within 14 days prior to registration: Absolute neutrophil count (ANC) >= 1,500/mcl
  • Within 14 days prior to registration: Hemoglobin (Hgb) >= 9 g/dL
  • Within 14 days prior to registration: Serum creatinine =< 1.5 x upper limit of normal (ULN)
  • Within 14 days prior to registration: Aspartate aminotransferase (AST)/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)
  • 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

Exclusion Criteria:

  • Prior treatment with an investigational EZH2 inhibitor
  • Patients whose circumstances do not permit completion of the study or the required follow-up
  • Patients who are unable to swallow pills
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years, with the exception of those with a negligible risk of metastases or death, such as carcinoma in situ of the breast or cervix
  • Severe, active co-morbidity defined as follows:

    • Life expectancy < 3 months
  • Pregnant or lactating patients
  • Human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
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
United States, Pennsylvania
NRG Oncology Recruiting
Philadelphia, Pennsylvania, United States, 19103
Contact: Ramez N. Eskander    858-822-6199    reskander@ucsd.edu   
Principal Investigator: Ramez N. Eskander         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ramez Eskander NRG Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03348631     History of Changes
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 Submitted: November 20, 2017
First Posted: November 21, 2017
Last Update Posted: November 21, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Endometrioid
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Endometrial Neoplasms
Uterine Neoplasms