Lurbinectedin for Ewing Sarcoma

(LiFFT Trial)

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Theodore W. Laetsch

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Children's Hospital of Philadelphia

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Brain metastases, Bleeding diathesis, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of 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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take certain investigational drugs, anticancer agents, or strong/moderate CYP3A4 inhibitors or inducers within 14 days before starting the study drug.

How is the drug Lurbinectedin different from other treatments for Ewing Sarcoma?

Lurbinectedin is unique because it works by inhibiting the transcription process in cancer cells, which is different from the traditional chemotherapy drugs used for Ewing Sarcoma that typically target cell division. This novel mechanism may offer a new approach for treating this condition. ^{1 2 3 4 5}

Research Team

Theodore W. Laetsch

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for people aged 10 and older with certain types of sarcoma, including Ewing Sarcoma, that have come back or didn't respond to initial treatment. Participants need measurable disease, adequate organ function, and must not be pregnant or breastfeeding. They should agree to use birth control and meet specific recovery criteria from previous treatments.

Inclusion Criteria

My cancer has returned or didn't respond to initial treatment and has a specific genetic change.

Time elapsed from previous therapy requirements

I can care for myself and am up and about more than half of my waking hours.

Exclusion Criteria

I do not have any severe illnesses or infections that are not under control.

Pregnant or breastfeeding

I have a known bleeding disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lurbinectedin on a day 1, 4 schedule to test safety, tolerability, and pharmacokinetics in FET-fusion tumors

Approximately 1 year

Every 2 to 4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and response assessments

28 days after last dose

Long-term Follow-up

Participants are monitored for disease control, progression-free survival, and overall survival

Up to 5 years

Treatment Details

Interventions

• Lurbinectedin (Alkylating agents)

Trial Overview The study is testing the safety and effectiveness of a drug called lurbinectedin in treating recurrent or relapsed solid tumors. It focuses on patients whose tumors have specific genetic features known as FET fusions.

Participant Groups

Group I: Ewing Sarcoma Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Joseph W. St. Geme III

Children's Hospital of Philadelphia

Chief Medical Officer since 2021

MD, PhD, MPH

Madeline Bell

Children's Hospital of Philadelphia

Chief Executive Officer since 2015

BSc in Nursing from Villanova University, MSc in Organizational Dynamics from the University of Pennsylvania

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Findings from Research

In a study involving 851 patients with Ewing tumors receiving 4,746 courses of the VIDE chemotherapy regimen, the most common adverse reactions were myelosuppression and infections, but these were manageable with supportive therapy, allowing for the maintenance of targeted dose intensity.

Age and gender significantly influenced the severity of hematotoxicity, with younger patients and females experiencing more severe effects, while the use of G-CSF did not significantly reduce the rates of neutropenia-related fever and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. Juergens, C., Weston, C., Lewis, I., et al.[2022]

The Scandinavian Sarcoma Group's treatment of 140 Ewing's sarcoma patients showed improved outcomes with the SSG IX protocol, resulting in a lower local recurrence rate (10%) and better tumor-related survival (70%) compared to the earlier SSG IV protocol (19% recurrence and 49% survival).

Patients with localized extremity tumors treated under SSG IX had an impressive survival rate of 90%, highlighting the effectiveness of this protocol, especially for specific tumor locations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience. Elomaa, I., Blomqvist, C., Saeter, G., et al.[2014]

The combination of low-dose vinblastine and celecoxib with standard chemotherapy for metastatic Ewing sarcoma was feasible, with 90% of patients receiving at least 75% of the planned doses and no significant increase in common toxicities.

However, there were concerns about increased pulmonary toxicity in patients who received radiation, leading to serious complications, including two deaths, which limits the protocol's overall safety and usefulness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893. Felgenhauer, JL., Nieder, ML., Krailo, MD., et al.[2021]

In a study of 177 patients with localized Ewing's sarcoma, the overall 5-year survival rate was 69%, with local control being highest after radical surgery (100%) and resection plus radiotherapy (95%).

Both hyperfractionated split-course irradiation and conventional fractionation provided similar outcomes in terms of survival and local control, indicating that the type of radiation fractionation may not significantly impact treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy in Ewing's sarcoma: an update of the CESS 86 trial. Dunst, J., Jürgens, H., Sauer, R., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. [2022]

2. Sweden pubmed.ncbi.nlm.nih.gov

Chemotherapy in Ewing's sarcoma. The Scandinavian Sarcoma Group experience. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Radiation therapy in Ewing's sarcoma: an update of the CESS 86 trial. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe. [2022]