Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma
- Conditions
- Advanced Soft-tissue SarcomaAdvanced Epithelioid Sarcoma
- Interventions
- Registration Number
- NCT04204941
- Lead Sponsor
- Epizyme, Inc.
- Brief Summary
The participants of this study will have advanced epithelioid sarcoma. Sarcoma is a cancer of the connective tissues, such as nerves, muscles and bones. Epithelioid sarcoma is an ultra-rare sarcoma of the soft-tissue.
Part 1 of this trial will evaluate the safety and the level of the study drug that the study drug combinations can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for the next part of the study.
Part 2 will evaluate and compare for each of the study drug combinations how long participants live without their disease getting worse.
The study drug is called tazemetostat. The study will test tazemetostat in combination with doxorubicin compared to placebo (dummy treatment) in combination with doxorubicin. Doxorubicin is a current front line treatment for epithelioid sarcoma
- Detailed Description
The open-label phase 1b portion is designed to evaluate the safety of the combination of tazemetostat + doxorubicin, as well as to establish the maximum tolerated dose (MTD) and the RP3D. The phase 3 portion of the clinical trial aims to compare tazemetostat + doxorubicin to the current front-line standard treatment, single-agent doxorubicin + placebo, when used as first-line treatment in locally advanced unresectable or metastatic ES.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 164
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1b: Open-label Tazemetostat and Phase 3: Tazemetostat + Doxorubicin Arm Doxorubicin HCl Phase 1b: On cycle 1 day -1, participants will receive a single morning dose of tazemetostat at the assigned dose level. Participants will receive doxorubicin 75 mg/m2 intravenously (IV) on day 1 of each cycle for up to 6 cycles. Tazemetostat will be escalated from a starting dose of 400 mg twice daily PO to 600 mg twice daily PO to 800 mg twice daily. Phase 3: Tazemetostat (800 mg) administered orally twice daily in continuous 21-day cycles during cycles 1-6 and in continuous 28-day cycles during cycle 7 and beyond. Doxorubicin 75 mg/m2 IV on day 1 of cycles 1-6. Phase 3: Placebo + Doxorubicin Arm Placebo Placebo administered orally twice daily in continuous 21-day cycles during cycles 1-6 and in continuous 28-day cycles during cycles 7 and beyond. Doxorubicin 75 mg/m2 IV on day 1 of cycles 1-6. Phase 3: Placebo + Doxorubicin Arm Doxorubicin HCl Placebo administered orally twice daily in continuous 21-day cycles during cycles 1-6 and in continuous 28-day cycles during cycles 7 and beyond. Doxorubicin 75 mg/m2 IV on day 1 of cycles 1-6. Phase 1b: Open-label Tazemetostat and Phase 3: Tazemetostat + Doxorubicin Arm Tazemetostat Phase 1b: On cycle 1 day -1, participants will receive a single morning dose of tazemetostat at the assigned dose level. Participants will receive doxorubicin 75 mg/m2 intravenously (IV) on day 1 of each cycle for up to 6 cycles. Tazemetostat will be escalated from a starting dose of 400 mg twice daily PO to 600 mg twice daily PO to 800 mg twice daily. Phase 3: Tazemetostat (800 mg) administered orally twice daily in continuous 21-day cycles during cycles 1-6 and in continuous 28-day cycles during cycle 7 and beyond. Doxorubicin 75 mg/m2 IV on day 1 of cycles 1-6.
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicities (DLTs) 1 Cycle/21 days Determined by Adverse Events (AEs) and clinical laboratory tests.
Progression free survival (PFS) Through study completion, an average of two years. Phase 3: Assessed by Independent Review Committee.
- Secondary Outcome Measures
Name Time Method Phase 1b: Pharmacokinetics (PK) of tazemetostat when administered in combination with doxorubicin in participants with soft tissue sarcoma (STS): Area under the Plasma Concentration Time Curve from time 0 to 24 hours (AUC0-24) Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy Phase 1b: PK of tazemetostat when administered in combination with doxorubicin in participants with STS: Area under the Plasma Concentration Time Curve From time 0 to the last observable concentration (AUC0- last) Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy Phase 1b: PK of tazemetostat when administered in combination with doxorubicin in Pparticipants with STS: The maximum observed concentration (Cmax). Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy Phase 3: Overall Survival (OS) Through study completion, an average of two years. Phase 3: Incidence of Adverse Events (AEs) Through study completion, an average of two years. All AEs, including clinically significant laboratory parameters will be graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE)
Phase 3: PFS Through study completion, an average of two years. Assessed by the investigator
Disease control rate (DCR) Through study completion, an average of two years Defined as the number of participants who achieve response complete response (CR) + partial response (PR) or who have stable disease (SD)
Objective response rate (ORR) Through study completion, an average of two years ORR is defined as the proportion of participants achieving complete or partial response. Determined based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Duration of treatment (DOR) Through study completion, an average of two years Defined as the time from first documented evidence of CR or PR to the time of first documented disease progression or death, whichever occurs first
Change from baseline in European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQC-30) Through study completion, an average of two years The EORTC QLQC-30 physical function, role function, and global health status domains will be assessed
PFS2 Through study completion, an average of two years Defined as time from randomization to objective tumor progression on next-line treatment or death, whichever occurs first
Time to first subsequent anti-cancer therapy ((TFST Through study completion, an average of two years Defined as the time from randomization to the time to first subsequent therapy
Population PK parameters of tazemetostat when administered in combination with doxorubicin: Oral clearance (CL/F) Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy CL/F is defined as the apparent oral clearance following administration of tazemetostat when administered in combination with doxorubicin
Population PK parameters of tazemetostat when administered in combination with doxorubicin: oral volume of distribution (Vss). Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy Population PK parameters of tazemetostat when administered in combination with doxorubicin: Area Under the Curve at steady state (AUCss) Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy Population PK parameters of tazemetostat when administered in combination with doxorubicin: trough concentration (Ctrough) Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy Population PK parameters of tazemetostat when administered in combination with doxorubicin: Cmax Cycles 1, 2, 3, and 5 of the first continuous 21-day cycles of combination therapy
Trial Locations
- Locations (21)
Sarcoma Oncology Research Center
🇺🇸Santa Monica, California, United States
University of Pittsburgh Medical Center - Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Mayo Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
McGill University Faculty of Medicine - Royal Victoria Hospital
🇨🇦Montréal, Quebec, Canada
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Insititute
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Fred Hutchinson Research Center
🇺🇸Seattle, Washington, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
Sarah Cannon and HCA Research Institute
🇺🇸Nashville, Tennessee, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Royal Marsden Foundation Trust
🇬🇧London, United Kingdom