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RECRUITINGPHASE1/PHASE2

Lurbinectedin in FET-Fused Tumors

Lurbinectedin in FET-Fusion Tumors (LIFFT)

NCT05918640•Children's Hospital of Philadelphia

Summary

The purpose of this study is to find out if a drug called lurbinectedin (the "study drug") is safe and effective at treating people with recurrent or relapsed solid tumors, including Ewing sarcoma.

Detailed Description

In this study, the investigators will test the activity of lurbinectedin as a targeted therapy for FET (FUS, Ewing Sarcoma Breakpoint Region 1 (EWRS1), TATA-Box-Binding Protein Associated Factor 15 (TAF15)). Ewing sarcoma is driven by the Ewing Sarcoma-Friend Leukemia Integration 1 Transcription Factor (EWS-FLI1). Lurbinectedin has been shown to inhibit EWS-FLI1 and Ewing Sarcoma-Wilms' Tumor Gene 1 (EWS-WT1) in preclinical models. Therefore, the goal of this study is to see if Lurbinectedin can be used to inhibit EWS-FLI1, EWS-WT1, or other FET fusion proteins to drive tumor responses in patients.

Eligibility

Age

10 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Age ≥ 10 years.
•2. Phase 1: Histological confirmed diagnosis of recurrent or relapsed solid tumor failing primary therapy. Patients must have a known FET fusion (fusion that contains EWSR1, FUS, or TAF15) as documented by next generation sequencing, polymerase chain reaction (PCR) or Fluorescence in situ hybridization (FISH). Patients with a histological diagnosis of Ewing sarcoma with EWS-FLI1 are eligible for dose escalation but not for the exploratory cohort. Please note patients with Ewing sarcoma and alternative FET-ETS fusions (including but not limited to EWS-ERG, EWS-ETV1, EWS-ETV4, EWS-FEV, FUS-ERG, FUS-FEV) are eligible for the exploratory cohort.
•3. Phase 2: Histologically confirmed diagnosis of recurrent or relapsed Ewing sarcoma failing primary therapy with confirmation of EWS-FLI1 fusion and breakpoint by Next generation sequencing or PCR or EWSR1 rearrangement confirmed by FISH and available tissue for central confirmation of EWS-FLI1 fusion and breakpoint.
•4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (age ≥16 years) or Lansky of at least 70 (age \<16 years).
•5. Disease status (baseline imaging must be performed within 28 days of Day 1 of study treatment):
•1. Phase 1: At least one site of measurable disease on CT or MRI as defined by RECIST 1.1 OR evaluable disease with at least one site of disease that has not been previously radiated
•2. Phase 2: At least one site of measurable disease on CT or MRI as defined by RECIST 1.1
•6. Meets organ function requirements as outlined below:
•1. Liver:
•Alanine aminotransferase (ALT) ≤ 2.5X upper limit of normal. For the purposes of this study the upper limit of normal for ALT is 45 U/L. Aspartate aminotransferase (AST) ≤ 2.5X upper limit of normal. For the purposes of this study the upper limit of normal for AST is 50 U/L. Total bilirubin ≤ 1.5X institutional upper limit of normal with the exception of patients with Gilbert's syndrome who must have bilirubin \<3X institutional upper limit of normal.
+20 more criteria

Exclusion Criteria

•1. Prior therapy with trabectedin or lurbinectedin.
•2. Subjects with known brain metastases.
•3. Subjects with a known bleeding diathesis.
•4. Subjects who are pregnant or breastfeeding.
•5. Concurrent therapy:
•1. Patients who are currently receiving an investigational drug or another anticancer agent
•2. Patients receiving over the counter or herbal supplement with significant potential hepatotoxicity in the opinion of the investigator.
•3. Patients receiving a medically necessary strong or moderate CYP3A4 inhibitor or inducer within 14 days prior to the first dose of study drug.
•6. Clinically significant, unrelated illness or uncontrolled infection which would, in the opinion of the treating physician, compromise the patient's ability to tolerate the investigational agents or be likely to interfere with the study procedures or results.
•7. Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
+2 more criteria

Locations (6)

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Key Dates

Start Date

July 27, 2023

Primary Completion Date

July 30, 2027

Completion Date

July 30, 2028

Last Updated

February 23, 2026

Enrollment

ESTIMATED participants

Conditions

Ewing SarcomaDesmoplastic Small Round Cell TumorPediatric CancerUndifferentiated Sarcoma

Interventions

Lurbinectedin

DRUG

Contacts

Theodore Laetsch, MD

CONTACT

267-425-5544 LAETSCHT@chop.edu

Meghan Donnelly

CONTACT

267-426-9343 22DT011@CHOP.EDU

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 23, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Lurbinectedin in FET-Fused Tumors

Inclusion Criteria

Exclusion Criteria

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