A Study to Assess the Long-term Safety of Tazemetostat

Advanced Solid Tumors Clinical Trial

— TRuST  

Official title:

Tazemetostat Rollover Study (TRuST): An Open-Label, Rollover Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02875548
• Other study ID #: EZH-501
• Secondary ID: 2015-004984-35
• Status: Enrolling by invitation
• Phase: Phase 1/Phase 2
• Start date: August 30, 2016
• Est. completion date: November 3, 2025

Study information

• Verified date: April 2024
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will provide continuing availability to tazemetostat for people that have previously completed participation in a tazemetostat study, either with monotherapy (single drug treatment) or combination therapy. The aim of the study will be to assess the long-term safety of tezemetostat.

Description:

This open-label, multicenter, global study will provide continuing access to tazemetostat therapy for subjects who have completed their participation in a prior tazemetostat study (either with monotherapy or combination therapy) without unacceptable toxicity, have not had evidence of tumor progression as defined by disease-appropriate standard criteria, and continue to receive clinical benefit from the therapy. Subjects will receive tazemetostat as dictated in their antecedent study. Visits will be conducted per Standard of Care (SoC) as appropriate in each country and as determined by the Investigator. Subjects will be followed for long-term safety in addition to time to treatment failure (TTF) and overall survival (OS).

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: November 3, 2025
• Est. primary completion date: November 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects must meet ALL criteria to be eligible for enrollment in this study.

2. Has demonstrated and continues to demonstrate clinical benefit from treatment with tazemetostat.

3. Is currently receiving tazemetostat as either monotherapy or in combination with other approved drug(s) or investigational agent(s) on an Epizyme-sponsored clinical trial or any other clinical trial being conducted with tazemetostat that is not sponsored by Epizyme (including but not limited to, investigator-initiated trials). For subjects on combination therapy, treatment with other therapeutic(s) must have been completed in the antecedent study or will be provided by a source other than Epizyme if combination therapeutics are continued in this study until disease progression, treatment toxicity, subject preference or death, up to approximately 7 years.

4. Has voluntarily provided signed written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol.

5. Has a life expectancy of =3 months.

6. Has adequate hematologic, (bone marrow [BM] and coagulation factors), renal, and hepatic function. Subject must remain eligible for continued treatment with tazemetostat according to the eligibility and treatment criteria from the antecedent study Exclusion Criteria:

Subjects meeting ANY of the following criteria must NOT be enrolled in this study:

1. Has had an interruption of tazemetostat dosing of >14 days from the antecedent clinical study to starting the rollover study unless approved by the Medical Monitor.

2. Has another malignancy other than the one for which they are receiving tazemetostat.

• Exception: Subject who has been disease-free of a prior malignancy for 5 years or subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible.

3. Has thrombocytopenia, neutropenia, or anemia of Grade =3 (per CTCAE v5 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).

4. Has a prior history of T-LBL/T-ALL.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Diffuse Large B-cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Mesothelioma
• Non-Hodgkin Lymphoma (NHL)
• Renal Medullary Carcinoma
• Sarcoma
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

Drug:
• Tazemetostat
Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of enhancer of Zeste homolog 2 (EZH2), a histone-lysine N-methyltransferase enzyme.

Locations

Country	Name	City	State
Australia	Monash Medical Centre- Monash Campus	Clayton
Australia	Geelong Hospital	Geelong
Australia	Peter MacCallum Cancer Institute	Melbourne
Belgium	University Hospital (UZ) Leuven	Leuven
France	Institut Bergonie	Bordeaux Cedex
France	CHU de Caen - Hôpital Côte de Nacre	Caen
France	CHRU de Lile- Hopital Claude Huriez	Lille Cedex
France	Hôpital Saint Louis - AP-HP	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	CHU Rennes- Hopital Pontchaillou	Rennes Cedex
France	Centre Henri Becquerel	Rouen
France	Gustave Roussay	Villejuif
Poland	Pratia MCM Krakow	Kraków
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Endokrynologii Onkologicznej i Medycyny Nuklearnej	Warszawa
Ukraine	S.P. Grigoreva Institute of Medical Radiology and Oncology of NAMS of Ukraine"	Kharkiv
United Kingdom	Beatson, West of Scotland Cancer Centre	Glasgow
United Kingdom	Oncology and Haematology Clinical Trials Unit	Leicester
United Kingdom	Clatterbridge Cancer Centre	Liverpool
United Kingdom	Hammersmith Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	University of Michigan	Ann Arbor	Michigan
United States	Columbia University Medical Center	New York	New York
United States	Moffitt	Tampa	Florida
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Epizyme, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Poland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs) and Treatment Emergent Adverse Event (TEAEs)	An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention Severity of adverse events experienced by all participants will be evaluated by the Investigator based on the CTCAE, version 5.0.	Until end of study an average of 7 years
Primary	Duration of Study Drug Exposure	The average study drug exposure duration will be reported.	Until end of study an average of 7 years
Secondary	The overall survival (OS)	Defined as the interval of time between the date of the first dose of tazemetostat and the date of death due to any cause	Until end of study an average of 7 years