RECRUITING

Lurbinectedin in FET-Fused Tumors

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Lurbinectedin in FET-Fusion Tumors (LIFFT)

Quick Facts

Study Start:2023-07-27

Study Completion:2028-07-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05918640

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:10 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 0-2 (age ≥16 years) or Lansky of at least 60 (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: 2. Renal: 3. Bone marrow: 4. Cardiac: 7. Written, voluntary informed consent 8. Fertile males and females of childbearing potential must agree to use an effective method of birth control from screening, through Day 1 of study and for 6 months after last study drug administration for females and 4 months for males. Women of childbearing potential must have a negative pregnancy test during screening procedures. Effective methods of birth control include: double barrier method (condom, diaphragm), abstinence, an intrauterine device (IUD), levonorgestrol implants, medroxyprogesterone acetate injections, or oral contraception. For those subjects whose preferred and usual lifestyle employs abstinence, refraining from heterosexual intercourse must be practiced during the entire active phase of the trial. 9. Patients ≥18 years must be willing to undergo tumor biopsy at study entry. Patients with Ewing sarcoma or DSRCT must be willing to undergo biopsy post-treatment. If biopsy is contraindicated, enrollment must be approved by study PI and archival tissue must be available. 10. Time elapsed from previous therapy: 1. Must be ≥ 3 weeks for systemic myelosuppressive therapy 2. ≥ 2 weeks for local radiation therapy (small field), ≥ 150 days after thyrotropin binding inhibition (TBI), craniospinal external beam radiotherapy (XRT) or radiation to ≥50% of the pelvis 3. ≥ 2 weeks for major surgery 4. ≥ 2 weeks for monoclonal antibodies and oral kinase inhibitors. 5. ≥ 6 weeks for autologous stem cell transplant. 6 months for allogeneic stem cell transplant. 6. ≥ 6 weeks for any type of cellular therapy 11. Patients must be recovered to baseline or Grade ≤1from the acute adverse effects of prior treatments, with the exception of alopecia and decreased deep tendon reflexes.	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. 8. Patients with known active viral hepatitis (i.e. Hepatitis A, B, or C)

Inclusion Criteria

Exclusion 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 0-2 (age ≥16 years) or Lansky of at least 60 (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:
2. Renal:
3. Bone marrow:
4. Cardiac:
7. Written, voluntary informed consent
8. Fertile males and females of childbearing potential must agree to use an effective method of birth control from screening, through Day 1 of study and for 6 months after last study drug administration for females and 4 months for males. Women of childbearing potential must have a negative pregnancy test during screening procedures. Effective methods of birth control include: double barrier method (condom, diaphragm), abstinence, an intrauterine device (IUD), levonorgestrol implants, medroxyprogesterone acetate injections, or oral contraception. For those subjects whose preferred and usual lifestyle employs abstinence, refraining from heterosexual intercourse must be practiced during the entire active phase of the trial.
9. Patients ≥18 years must be willing to undergo tumor biopsy at study entry. Patients with Ewing sarcoma or DSRCT must be willing to undergo biopsy post-treatment. If biopsy is contraindicated, enrollment must be approved by study PI and archival tissue must be available.
10. Time elapsed from previous therapy:
1. Must be ≥ 3 weeks for systemic myelosuppressive therapy
2. ≥ 2 weeks for local radiation therapy (small field), ≥ 150 days after thyrotropin binding inhibition (TBI), craniospinal external beam radiotherapy (XRT) or radiation to ≥50% of the pelvis
3. ≥ 2 weeks for major surgery
4. ≥ 2 weeks for monoclonal antibodies and oral kinase inhibitors.
5. ≥ 6 weeks for autologous stem cell transplant. 6 months for allogeneic stem cell transplant.
6. ≥ 6 weeks for any type of cellular therapy
11. Patients must be recovered to baseline or Grade ≤1from the acute adverse effects of prior treatments, with the exception of alopecia and decreased deep tendon reflexes.

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.
8. Patients with known active viral hepatitis (i.e. Hepatitis A, B, or C)

Contacts and Locations

Study Contact

Theodore Laetsch, MD

CONTACT

267-425-5544

LAETSCHT@chop.edu

Meghan Donnelly

CONTACT

267-426-9343

22DT011@CHOP.EDU

Principal Investigator

Theodore Laetsch, MD

PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Study Locations (Sites)

Cedars-Sinai Medical Center

Los Angeles, California, 90048

United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

United States

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Michigan

Ann Arbor, Michigan, 48109

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: Children's Hospital of Philadelphia

Theodore Laetsch, MD, PRINCIPAL_INVESTIGATOR, Children's Hospital of Philadelphia

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-27

Study Completion Date2028-07-30

Study Record Updates

Study Start Date2023-07-27

Study Completion Date2028-07-30

Terms related to this study

Keywords Provided by Researchers

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)

Additional Relevant MeSH Terms

Ewing Sarcoma
Desmoplastic Small Round Cell Tumor
Pediatric Cancer
Undifferentiated Sarcoma