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Phase II Study of Tazemetostat in Solid Tumors Harboring an ARID1A Mutation

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.
 
ClinicalTrials.gov Identifier: NCT05023655
Recruitment Status : Recruiting
First Posted : August 26, 2021
Last Update Posted : February 17, 2022
Sponsor:
Collaborator:
Epizyme, Inc.
Information provided by (Responsible Party):
Prisma Health-Upstate

Brief Summary:
The FDA approved targeted agent tazemetostat inhibits EZH2 and induces durable tumor responses in patients with B-cell non-Hodgkin's lymphoma and epithelioid sarcomas. Responses have also been demonstrated in INI1 and SMARCA4 negative solid tumors patients. Since EZH2 plays a critical role in driving the biology of ARID1A mutated malignancies, we hypothesize that inhibition of EZH2 with tazemetostat will lead to significant clinical benefit in ARID1A mutated malignancies.

Condition or disease Intervention/treatment Phase
Solid Tumor ARID1A Gene Mutation Drug: Tazemetostat Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Tazemetostat in Solid Tumors Harboring an ARID1A Mutation
Actual Study Start Date : January 6, 2022
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tazemetostat
tazemetostat 800 mg po twice daily in continuous 28- day cycles
Drug: Tazemetostat
800mg po twice daily
Other Name: tazverik




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: through study completion, estimated to be 1 year after the last subject enrolled ]
    Evidence of anti-tumor activity will be assessed by objective response, as defined by RECIST 1.1. This will be used to summarize ORR (CR+PR), as well as the rates for the individual categories of response, (i.e., CR, PR, SD, and PD).


Secondary Outcome Measures :
  1. Disease Control Rate [ Time Frame: through study completion, estimated to be 1 year after the last subject enrolled ]
    DCR defined as the proportion of subjects with best overall response of CR, PR, or SD lasting 3 or more months.



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.


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

Inclusion Criteria:

  • Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.
  • Histologically and/or cytologically confirmed advanced or metastatic solid tumor harboring ARID1A mutation (except epithelioid sarcoma)
  • Progression of disease following approved therapies or for which no standard therapy exists
  • For subjects who have experienced any clinically significant toxicity related to a prior anticancer treatment (i.e., chemotherapy, immunotherapy, and/or radiotherapy): at the time the subject provides voluntary written informed consent, all toxicities have either resolved to grade 1 per NCI CTCAE Version 5.0 [11] OR are clinically stable and no longer clinically significant.
  • Have measurable disease as defined by RECIST 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Males or females are >18 years of age at the time of providing voluntary written informed consent.
  • Life expectancy >3 months before enrollment.
  • Time between prior anticancer therapy and first dose of tazemetostat as follows:

Cytotoxic chemotherapy - At least 21 days Noncytotoxic chemotherapy (e.g., small molecule inhibitor) - At least 14 days. Nitrosoureas - At least 6 weeks. Monoclonal antibody - At least 28 days. Radiotherapy - At least 14 days. In addition, at least 6 weeks from prior radioisotope therapy; and at least 12 weeks from 50% pelvic or total body irradiation.

  • Adequate renal function: Creatinine < 2.0 or calculated creatinine clearance ≥ 35 mL/minute per the Cockcroft and Gault formula
  • Adequate bone marrow function:

ANC ≥ 750mm3 without growth factor support (filgrastim or pegfilgrastim) for at least 14 days.

Platelets ≥ 75,000mm3 (≥75 × 109/L) evaluated at least 7 days after platelet transfusion.

Hemoglobin ≥9.0 g/dL and may receive transfusion Adequate liver function: Total bilirubin <1.5 × the upper limit of normal (ULN) (except for unconjugated hyperbilirubinemia of Gilbert's syndrome); Alkaline phosphatase (ALP) (in the absence of bone disease), ALT, and AST <3 × ULN (or <5 × ULN if subject has liver metastases).

Exclusion Criteria:

  • Subjects with epithelioid sarcoma are excluded.
  • Has a prior history of T-Cell Lymphoblastic Lymphoma, T-Cell Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Acute Myeloid Leukemia, or Myeloproliferative Neoplasm.
  • Female subjects who are pregnant or breastfeeding.
  • Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
  • Subjects with uncontrolled CNS metastases requiring steroids.
  • Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's wort)
  • Are unwilling to exclude Seville oranges, grapefruit juice, AND grapefruit from their diet.
  • Major surgery within 4 weeks before the first dose of study drug. NOTE: Minor surgery (e.g., minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 1 week prior to enrollment.
  • Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.
  • Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II (Appendix 3), uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.
  • Have an active infection requiring systemic therapy.
  • Known hypersensitivity to any component of tazemetostat.
  • Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
  • Subjects who have undergone a solid organ transplant.
  • Prior malignancy in the past 5 years.

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): NCT05023655


Contacts
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Contact: Julie C Martin, DNP 864-455-3667 julie.martin@prismahealth.org
Contact: Jan Kueber, MBA 864-455-3774 jan.kueber@prismahealth.org

Locations
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United States, South Carolina
Prisma Health Cancer Institute Recruiting
Greenville, South Carolina, United States, 29605
Contact: Lisa M Johnson, RN    864-455-3735    lisa.johnson@prismahealth.org   
Contact: Fiona Davidson, RN    864-455-3737    fiona.davidson@prismahealth.org   
Principal Investigator: Ki Chung, MD         
Sub-Investigator: William J Edenfield, MD         
Sponsors and Collaborators
Prisma Health-Upstate
Epizyme, Inc.
Investigators
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Principal Investigator: Ki Chung, MD Prisma Health
Publications:

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Responsible Party: Prisma Health-Upstate
ClinicalTrials.gov Identifier: NCT05023655    
Other Study ID Numbers: EPZ-IST-001
First Posted: August 26, 2021    Key Record Dates
Last Update Posted: February 17, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: There is a plan to make data available once request is reviewed and approved by the investigators.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: beginning 6 months following publication of study results and ending 24 months post publication
Access Criteria: Data request must be submitted to the principal investigator, reviewed and approved by the study investigators.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prisma Health-Upstate:
ARID1A mutation; solid tumors; tazemetostat
Additional relevant MeSH terms:
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Neoplasms