Lurbinectedin in FET-Fused Tumors

NCT05918640 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 23-020814
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Pediatric Cancer; Undifferentiated Sarcoma; Desmoplastic Small Round Cell Tumor; Ewing Sarcoma

Keywords

Ewing Sarcoma-Friend Leukemia Integration 1 Transcription factor (ESW-FLI1); Ewing Sarcoma Breakpoint Region 1-Friend Leukemia Integration 1 Transcription factor (EWSR1-FLI1); Ewing Sarcoma Erythroblast Transformation Specific Related Gene (EWS-ERG); Ewing Sarcoma Breakpoint Region 1 (EWRS1); TATA-Box-Binding Protein Associated Factor 15 (TAF15); Fused Tumors (FET); Ewing Sarcoma-Wilms' Tumor Gene 1 (EWS-WT1)

Outcome Measures

Primary Outcomes (4)

• Phase 1: Dose Limiting Toxicities (DLTs)

  First cycle (approximately 21 days) Dose Limiting Toxicities (DLTs) will be evaluated.

  within 28 days of the first dose

• Phase 1: Frequency of adverse events

  Adverse events to be reported during treatment and for at least 28 days after last dose.

  28 days after last dose

• Phase 1: Complete Response or Partial Response

  Percentage of participants with complete response or partial response will be assessed approximately every 2 to 4 cycles through the end of treatment and up to at least 28 days after the last dose.

  through the end of treatment, an average of 1 year

• Phase 2: Event-Free Survival (EFS)

  Event-free survival (EFS) is based on investigator assessment from baseline until Month 24.

  2 years

Secondary Outcomes (6)

• Phase 1: Maximum observed Plasma Concentration (Cmax)

  at the end of cycle 1 (each cycle is 28 days)

• Phase 1: Area under the concentration-time curve (AUC)

  at the end of cycle 1 (each cycle is 28 days)

• Phase 2: 6-month Progression Free Survival (PFS)

  6 months

• Phase 1: Duration of Response (DoR)

  Up to 5 years

• Phase 2: Overall Survival

  Up to 5 years

Study Arms (1)

Ewing Sarcoma

EXPERIMENTAL

The first part of this study is a standard 3+3 design to test the safety, tolerability and pharmacokinetic profile of lurbinectedin administered on a day 1, 4 schedule in patients with FET-fusion tumors.

Drug: Lurbinectedin

Interventions

Lurbinectedin DRUG

Lurbinectedin will be administered on a Day 1, Day 4 schedule every 21 days. Doses will be determined in the phase 1 portion of the trial.

Ewing Sarcoma

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 10 years.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (age \>16 years) or Lansky of at least 70 (age \<16 years).
• Disease status (baseline imaging must be performed within 28 days of Day 1 of study treatment):
• 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
• Phase 2: At least one site of measurable disease on CT or MRI as defined by RECIST 1.1
• Meets organ function requirements as outlined below:
• 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.
• Renal:
• Creatinine Calculated creatinine clearance (by the Schwartz equation for patients \<18 years of age and Cockroft-Gault formula (Appendix B) for patients ≥18 years of age) or radionuclide glomerular filtration rate (GFR) ≥ 50 mL/min /m2 or a serum creatinine less than or equal to the age/gender valued below:
• Age Maximum Serum Creatinine (mg/dL) Male Female 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4
• ≥ 16 years 1.7 1.4
• Bone marrow:

You may not qualify if:

• Prior therapy with trabectedin or lurbinectedin.
• Subjects with known brain metastases.
• Subjects with a known bleeding diathesis.
• Subjects who are pregnant or breastfeeding.
• Concurrent therapy:
• Patients who are currently receiving an investigational drug or another anticancer agent
• Patients receiving over the counter or herbal supplement with significant potential hepatotoxicity in the opinion of the investigator.
• Patients receiving a medically necessary strong or moderate CYP3A4 inhibitor or inducer within 14 days prior to the first dose of study drug.
• 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.
• 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.
• Patients with known active viral hepatitis (i.e. Hepatitis A, B, or C)
• Patients with Desmoplastic small round cell tumor (DSRCT) will be excluded from enrollment until at least 3 non-DSRCT patients have been enrolled without dose limiting toxicity.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Jazz Pharmaceuticals: collaborator
• Stand Up To Cancer: collaborator

Study Sites (6)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma, Ewing; Desmoplastic Small Round Cell Tumor; Neoplasms

Interventions

PM 01183

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma

Study Officials

• Theodore Laetsch, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Theodore Laetsch, MD

CONTACT

267-425-5544; LAETSCHT@chop.edu

Meghan Donnelly

CONTACT

267-426-9343; 22DT011@CHOP.EDU

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first part of this study is a standard 3+3 design to test the safety, tolerability and pharmacokinetic profile of lurbinectedin administered on a day 1, 4 schedule in patients with FET-fusion tumors. The second part of this study is a single-stage phase 2 design and will accrue 17 patients in parallel to the exploratory cohort after the Recommended Phase 2 Dose (RP2D) is determined.

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: June 26, 2023
• Study Start: July 27, 2023
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)