Lurbinectedin in FET-Fused Tumors
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age10+
SponsorChildren's Hospital of Philadelphia
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
Prior therapy with trabectedin or lurbinectedin.
Subjects with known brain metastases.
Subjects with a known bleeding diathesis.
Subjects who are pregnant or breastfeeding.
Trial design
Design model
Single group
Treatments tested in this trial
Lurbinectedin
DrugLurbinectedin 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.
Treatment groups
63 Participants
are divided into 1 treatment groupGroup A: Ewing SarcomaExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Phase 1: Dose Limiting Toxicities (DLTs)
First cycle (approximately 21 days) Dose Limiting Toxicities (DLTs) will be evaluated.
Time frame
within 28 days of the first dose2
Phase 1: Frequency of adverse events
Adverse events to be reported during treatment and for at least 28 days after last dose.
Time frame
28 days after last dose3
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.
Time frame
through the end of treatment, an average of 1 year4
Phase 2: Event-Free Survival (EFS)
Event-free survival (EFS) is based on investigator assessment from baseline until Month 24.
Time frame
2 yearsSecondary outcomes
1
Phase 1: Maximum observed Plasma Concentration (Cmax)
Maximum observed plasma concentration (Cmax) will be used to assess Lurbinectedin Pharmacokinetics
Time frame
at the end of cycle 1 (each cycle is 28 days)2
Phase 1: Area under the concentration-time curve (AUC)
Area under the concentration-time curve (AUC) will be used to assess Lurbinectedin Pharmacokinetics
Time frame
at the end of cycle 1 (each cycle is 28 days)3
Phase 2: 6-month Progression Free Survival (PFS)
Progression Free Survival (PFS) assessed from the first dose of study drug to earliest date of death or progressive disease.
Time frame
6 months4
Phase 1: Duration of Response (DoR)
Duration of Response (DoR) defined as time from date of first response (Complete Response or Partial Response) in responders to date of progression or death
Time frame
Up to 5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Children's Hospital of Philadelphia
Lead sponsor
Jazz Pharmaceuticals
Collaborator
Stand Up To Cancer
Collaborator
Source ClinicalTrials.gov