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

• ClinicalTrials.gov Identifier: NCT03348631
• Recruitment Status: Suspended
• First Posted: November 21, 2017
• Last Update Posted: August 30, 2019
• Sponsor: National Cancer Institute (NCI)
• Collaborator: NRG Oncology
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma; FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma	Other: Laboratory Biomarker Analysis; 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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 43 participants
• 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
• Actual Study Start Date: March 29, 2019
• Estimated Primary Completion Date: January 31, 2025
• Estimated Study Completion Date: January 31, 2025

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. Tumor response in patients with ARID1A mutations using tumor response as defined by RECIST v 1.1 [ Time Frame: Up to 6 months ]
2. Incidence of adverse events according to grade of toxicity by organ or organ system [ Time Frame: Up to 5 years ]
3. 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.
4. 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.

Eligibility Criteria

• 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/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

  Show 419 Study Locations

Sponsors and Collaborators

National Cancer Institute (NCI)

NRG Oncology

Investigators

• Principal Investigator: Ramez N 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 Posted: November 21, 2017
• Last Update Posted: August 30, 2019
• Last Verified: August 2019

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

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

Additional relevant MeSH terms:

Carcinoma; Adenocarcinoma; Carcinoma, Endometrioid; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian 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