Ovarian Cancer Clinical Trial

A Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma

Summary

This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID (twice daily) and 1600 mg QD (once daily). Subjects will be screened for eligibility within 21 days of the planned date of the first dose of tazemetostat and enrolled into one of 8 cohorts:

Cohort using tazemetostat 800 mg BID

Cohort 1 (Closed for enrollment): MRT, RTK, ATRT, and selected tumors with rhabdoid features, including small cell carcinoma of the ovary hypercalcemic type [SCCOHT], also known as malignant rhaboid tumor of the ovary [MRTO]
Cohort 2 (Closed for enrollment): Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement
Cohort 3 (Closed for enrollment): Other INI1 negative tumors or any solid tumor with an EZH2 gain of function (GOF) mutation, including: epithelioid malignant peripheral nerve sheath tumor (EMPNST), extraskeletal myxoid chondrosarcoma (EMC), myoepithelial carcinoma, other INI1-negative malignant tumors with Sponsor approval (e.g., dedifferentiated chordoma) any solid tumor with an EZH2 GOF mutation including but not limited to Ewing's sarcoma and melanoma
Cohort 4 (Closed for enrollment): Renal medullary carcinoma (RMC)
Cohort 5 (Closed for enrollment): Epithelioid sarcoma (ES)
Cohort 6 (Opened for enrollment): Epithelioid sarcoma (ES) undergoing mandatory tumor biopsy
Cohort 7 (Closed for enrollment): Poorly differentiated chordoma (or other chordoma with Sponsor approval)

Cohort using tazemetostat 1600 mg QD

• Cohort 8 (Closed for enrollment): Epitheliod sarcoma

Subjects will be dosed in continuous 28-day cycles. (Note: if treatment with study drug is discontinued prior to completing 2 years, subjects will be followed for a maximum duration of 2 years from start of study drug dosing.) Response assessment will be performed every 8 weeks while on study.

Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study.

View Full Description

Full Description

This is a Phase II, multicenter, open-label, single arm, 2-stage study of tazemetostat 800 mg BID (twice daily) and 1600 mg QD (once daily). Subjects will be screened for eligibility within 21 days of the planned date of the first dose of tazemetostat and enrolled into one of 8 cohorts:

Cohort using tazemetostat 800 mg BID

Cohort 1 (Closed for enrollment): malignant rhabdoid tumor (MRT), rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and selected tumors with rhabdoid features, including small cell carcinoma of the ovary hypercalcemic type (SCCOHT), also known as malignant rhaboid tumor of the ovary (MRTO)
Cohort 2 (Closed for enrollment): Relapsed or refractory synovial sarcoma with SS18-SSX rearrangement
Cohort 3 (Closed for enrollment): Other integrase interactor 1 (INI1) negative tumors or any solid tumor with an enhancer of zeste homologue-2 (EZH2) gain of function (GOF) mutation, including: epithelioid malignant peripheral nerve sheath tumor (EMPNST), extraskeletal myxoid chondrosarcoma (EMC), myoepithelial carcinoma, other INI1-negative malignant tumors with Sponsor approval (e.g., dedifferentiated chordoma) any solid tumor with an EZH2 GOF mutation including but not limited to Ewing's sarcoma and melanoma
Cohort 4 (Closed for enrollment): Renal medullary carcinoma (RMC)
Cohort 5 (Closed for enrollment): Epithelioid sarcoma (ES)
Cohort 6 (Closed for enrollment): Epithelioid sarcoma (ES) undergoing mandatory tumor biopsy
Cohort 7 (Closed for enrollment): Poorly differentiated chordoma (or other chordoma with Sponsor approval)

Cohort using tazemetostat 1600 mg QD

• Cohort 8 (Closed for enrollment): Epitheliod sarcoma

Participants will be dosed in continuous 28-day cycles. (Note: if treatment with study drug is discontinued prior to completing 2 years, subjects will be followed for a maximum duration of 2 years from start of study drug dosing.) Response assessment will be performed every 8 weeks while on study.

Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Age (at the time of consent/assent): ≥18 years of age
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Has provided signed written informed consent
Has a life expectancy of >3 months

Has a malignancy:

For which there are no standard therapies available (Cohorts 1, 3, 4 and 5)

That is relapsed or refractory after treatment with an approved therapy(ies), defined as metastatic or non-resectable, locally advanced disease that has previously been treated with and progressed following approved therapy(ies) (Cohort 2)

That has progressed within 6 months prior to study enrollment (Cohort 5 Expansion, Cohort 6 and Cohort 8 ONLY)
Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA/College of American Pathologists (CAP) or equivalent laboratory certification
For Cohort 1 (rhabdoid tumors only), the following test results must be available by local laboratory: morphology and immunophenotypic panel consistent with rhabdoid tumors, and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss or mutation when INI1 or SMARCA4 IHC is equivocal or unavailable
For Cohort 2 (subjects with relapsed/refractory synovial sarcoma only), the following tests must be available by local laboratory: Morphology consistent with synovial sarcomas, and cytogenetics or fluorescence in situ hybridization (FISH) and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11)
For Cohort 3, 4, 5, 7 and 8 (subjects with INI1-negative/aberrant tumors or any solid tumor with EZH2 GOF mutation only), the following test results must be available by local laboratory: Morphology and immunophenotypic panel consistent with INI1-negative tumors (not applicable for solid tumors with EZH2 GOF mutation), and loss of INI1 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 loss or mutation when INI1 IHC is equivocal or unavailable, or molecular evidence of EZH2 GOF mutation

For Cohort 6 (subjects with ES undergoing optional tumor biopsy) only:

Morphology and immunophenotypic panel consistent with ES (e.g., CD34, EMA, Keratin, and INI1)
Has all prior treatment (i.e. chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤Grade 1 per CTCAE version 4.0.3 or are clinically stable and not clinically significant, at time of enrollment.

Prior anti-cancer therapy(ies), if applicable, must be completed according to the criteria below:

Chemotherapy: cytotoxic (At least 14 days since last dose of chemotherapy prior to first dose of tazemetostat)
Chemotherapy: nitrosoureas (At least 6 weeks since last dose of nitrosoureas prior to first dose of tazemetostat)
Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) (At least 14 days since last dose of non-cytotoxic chemotherapy prior to first dose of tazemetostat)
Monoclonal antibody(ies) (At least 28 days since the last dose of any monoclonal antibody prior to first dose of tazemetostat)
Immunotherapy (e.g. tumor vaccine) (At least 42 days since last dose of immunotherapy agent(s) prior to first dose of tazemetostat)
Radiotherapy (RT) (At least 14 days from last local site RT prior to first dose of tazemetostat/At least 21 days from stereostatic radiosurgery prior to first dose of tazemetostat/At least 12 weeks from craniospinal, ≥50% radiation of pelvis, or total body irradiation prior to first dose of tazemetostat)
High dose therapy with autologous hematopoietic cell infusion (At least 60 days from last infusion prior to first dose of tazemetostat)
Hematopoietic growth factor (At least 14 days from last dose of hematopoietic growth factor prior to first dose of tazemetostat)
Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing
Has measurable disease based on either RECIST 1.1 for solid tumors or RANO for CNS tumors
Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function.
For subjects with CNS Tumors only, subject must have seizures that are stable, not increasing in frequency or severity and controlled on current anti-seizure medication(s) for a minimum of 21 days prior to the planned first dose of tazemetostat
Has a shortening fraction of >27% or an ejection fraction of ≥50% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan and New York Heart Association (NYHA) Class ≤2
Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec

Female subjects of childbearing potential must:

Have a negative beta-human chorionic gonadotropin (β-hCG) pregnancy test at time of screening and within 14 days prior to planned first dose of tazemetostat and
Agree to use effective contraception from a minimum of 7 days prior to first dose until 6 months following the last dose of tazemetostat and have a male partner who uses a condom, or
Practice true abstinence or have a male partner who is vasectomized

Male subjects with a female partner of childbearing potential must:

Be vasectomized, or
Agree to use condoms as defined in Section 8.6.2, from first dose of tazemetostat until 3 months following the last dose of tazemetostat, or
Have a female partner who is NOT of childbearing potential

Exclusion Criteria:

Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
Has participated in another interventional clinical study and received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the planned first dose of tazemetostat
Has known active CNS or any leptomeningeal metastasis of primary extra-cranial tumor.
Has had a prior malignancy other than the malignancies under study - EXCEPTION: A subject who has been disease-free for 5 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible
Has had major surgery within 3 weeks prior to enrollment
Has Thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS). Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and MPN (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing.
Has a prior history of T-LBL /T-ALL
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet
Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
Is currently taking any prohibited medication(s)
Has an active infection requiring systemic treatment
Is immunocompromised (i.e. has congenital immunodeficiency), including subjects known history of infection with human immunodeficiency virus (HIV)
Has known active infection with hepatitis B virus or hepatitis C virus
Has had a symptomatic venous thrombosis within 2 weeks prior to study enrollment -
For subjects with CNS involvement (primary tumor or metastatic disease), have any active bleeding or new intratumoral hemorrhage of more than punctuate size of screening MRI obtained within 14 days of starting study drug or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents
Has known hypersensitivity to any of the component of tazemetostat or other inhibitor(s)of EZH2
Is unable to take oral medications, or has a malabsorption syndrome or any uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that would limit compliance with study requirements.
Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements.
For female subjects of childbearing potential: Is pregnant or nursing
For male subjects: Is unwilling to adhere to contraception criteria from time of enrollment in the study to at least 3 months after last dose of tazemetostat.

Study is for people with:

Ovarian Cancer

Phase:

Phase 2

Estimated Enrollment:

267

Study ID:

NCT02601950

Recruitment Status:

Completed

Sponsor:

Epizyme, Inc.

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There are 32 Locations for this study

See Locations Near You

University of California San Francisco
San Francisco California, 94115, United States
University of Colorado Denver
Aurora Colorado, 80045, United States
Mayo Clinic - Jacksonville
Jacksonville Florida, 32224, United States
Northwestern Memorial Hospital
Chicago Illinois, 60611, United States
Massachusetts General Hospital - Cancer Center
Boston Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States
University of Michigan
Ann Arbor Michigan, 48109, United States
Washington University
Saint Louis Missouri, 63130, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
Cincinnati Children's Hospital Medical Center
Cincinnati Ohio, 45229, United States
Oregon Health Sciences University
Portland Oregon, 97239, United States
MD Anderson Cancer Center
Houston Texas, 77030, United States
Seattle Children's Hospital
Seattle Washington, 98105, United States
Fred Hutchinson Cancer Research Center
Seattle Washington, 98109, United States
Chris O'Brien Lifehouse
Camperdown New South Wales, 2050, Australia
Metro South Hospital and Health Service via Princess Alexandra Hospital
Woolloongabba , QLD 4, Australia
Institut Jules Bordet Medical Oncology Clinic
Brussels , 1000, Belgium
University Hospital Leuven
Leuven , 3000, Belgium
Alberta Health Services
Edmonton Alberta, T6G 1, Canada
Princess Margaret Hospital
Toronto Ontario, M5G 1, Canada
McGill University Health Centre - Royal Victoria Hospital
Montreal Quebec, H4A 3, Canada
Institut Bergonie
Bordeaux , 33076, France
Centre Leon Berard
Lyon , 69008, France
Hospital Pitie Salpetriere
Paris Cedex 13 , 75651, France
Institut Curie
Paris , 75248, France
Institut Gustave Roussy
Villejuif , 94800, France
Children's Hospital Augsburg Klinikum
Augsburg , 86156, Germany
Sarcoma Center HELIOS Klinikum Berlin
Berlin , 13125, Germany
Instituto Nazionale Tumori - National Cancer Institute Via Giacomo Venezian
Milano , 20133, Italy
National Taiwan University Hospital
Taipei City , 10002, Taiwan
University College London Hospital
London , NW1 2, United Kingdom
Royal Marsden Foundation Trust
London , SW3 6, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Ovarian Cancer

Phase:

Phase 2

Estimated Enrollment:

267

Study ID:

NCT02601950

Recruitment Status:

Completed

Sponsor:


Epizyme, Inc.

How clear is this clinincal trial information?

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