Lurbinectedin for Ewing Sarcoma

(LiFFT Trial)

Recruiting at 6 trial locations

Overseen By Theodore Laetsch, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital of Philadelphia

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Brain metastases, Bleeding diathesis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Approximately 1 year

63 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug, lurbinectedin, is safe and effective for treating certain cancers, such as Ewing sarcoma, that have recurred or resisted initial treatment. It targets individuals with specific genetic markers in their tumors, tailoring the treatment to their condition. Ideal candidates for this trial have Ewing sarcoma with recurring or resistant tumors and specific genetic markers identified in their cancer. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that lurbinectedin is likely to be safe for humans?

Research shows that lurbinectedin is generally well-tolerated by patients with relapsed Ewing sarcoma. Studies indicate that while some side effects occur, they are usually manageable, allowing doctors to help patients address them. Another study found that lurbinectedin has an acceptable safety profile for patients. This suggests that, despite some risks, the treatment is considered safe enough to continue exploring its benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lurbinectedin is unique because it targets Ewing Sarcoma through a novel mechanism of action. Unlike standard treatments that often involve chemotherapy drugs like vincristine, doxorubicin, and cyclophosphamide, lurbinectedin works by inhibiting the transcription process in cancer cells, effectively blocking their ability to multiply. Researchers are excited about lurbinectedin because it offers a new approach that might be more effective or have fewer side effects compared to existing options. Additionally, its administration on a day 1, 4 schedule could provide a more flexible treatment regimen for patients.

What evidence suggests that lurbinectedin might be an effective treatment for Ewing sarcoma?

Research has shown that lurbinectedin, the investigational treatment in this trial, may help treat certain cancers, such as Ewing sarcoma. In earlier studies, patients with solid tumors who received lurbinectedin experienced tumor shrinkage or slower growth. This drug blocks a process essential for cancer cell survival and multiplication. Although more data is needed, early signs suggest that lurbinectedin could benefit people with Ewing sarcoma that has recurred or not responded to other treatments. These are preliminary findings, and ongoing trials, including this one, aim to provide more information about its efficacy and safety. ^{1 2 4 6 7}

Who Is on the Research Team?

Theodore W. Laetsch

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lurbinectedin

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.

How Is the Trial Designed?

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.

Lurbinectedin is already approved in United States, European Union for the following indications:

Approved in United States as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Approved in European Union as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

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+

Published Research Related to This Trial

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]

Recent clinical trials for Ewing sarcoma have improved long-term disease-free survival rates to approximately 70% for patients with localized disease, highlighting the effectiveness of combined local therapies and cytotoxic drugs.

Ongoing interdisciplinary and international collaboration in translational research is crucial for developing new strategies to enhance cure rates and improve the quality of life for Ewing sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe. Bölling, T., Braun-Munzinger, G., Burdach, S., et al.[2022]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.11519

Efficacy and safety of lurbinectedin (PM1183) in Ewing ... The study treatment was lurbinectedin 3.2 mg/m2 in a 1-hour infusion every 3 weeks. Results: 28 evaluable pts were enrolled. Median age was 33 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05734066

NCT05734066 | Study of Lurbinectedin Monotherapy in ... The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9306456/

Antitumor Activity of Lurbinectedin, a Selective Inhibitor of ... First-line treatment with surgery, radiotherapy, and multi-agent chemotherapy has resulted in 5-year disease-free survival rates of 60% to 70% in patients with ...

4. nationwidechildrens.org nationwidechildrens.org/research/clinical-research/cancer-clinical-research/sarcoma-and-solid-tumor-studies/content/jzp712-101

Ewing Sarcoma Clinical Study The phase 1 portion of the study evaluates the safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and effectiveness of lurbinectedin ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT02454972

Clinical Trial of Lurbinectedin (PM01183) in Selected ... Comparative Effectiveness of Lurbinectedin for the Treatment of Relapsed Small Cell Lung Cancer ... (PM1183) in Ewing sarcoma: Final results from a phase 2 study.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35486638/

Results of a Basket Phase II Study - PubMed - NIH Lurbinectedin was active in the treatment of relapsed Ewing sarcoma and had a manageable safety profile. Lurbinectedin could represent a valuable addition to ...

7. pharmamar.com pharmamar.com/en/results-of-the-phase-ii-trial-with-lurbinectedin-for-the-treatment-of-patients-with-relapsed-ewing-sarcoma/

Results of the phase II trial with lurbinectedin ... In addition, other secondary endpoints such as a median Progression-Free Survival (PFS) of 2.7 months, a clinical benefit ratio of 39.3% and a ...