Lurbinectedin for Ewing Sarcoma

(EMERGE 101 Trial)

Recruiting at 16 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jazz Pharmaceuticals

Must not be taking: Steroids, Antibiotics, Antifungals, Antivirals

Disqualifiers: CNS metastases, Uncontrolled illness, HIV, 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: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lurbinectedin (Zepzelca) for young people with Ewing sarcoma, a type of cancer that recurs or resists other treatments. The first phase focuses on determining the safety and optimal dose for children with solid tumors. The second phase evaluates the treatment's effectiveness for those with Ewing sarcoma. Suitable participants are aged 2 to 30 and have experienced recurring Ewing sarcoma. As a Phase 1/Phase 2 trial, this research seeks to understand the treatment's effects and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received chemotherapy within 3 weeks before starting the study treatment, and you should not have taken any investigational products within 4 weeks of the first infusion.

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

Research has shown that lurbinectedin has been tested in people with advanced Ewing sarcoma, a type of bone cancer, and most patients handled the treatment well. One study found lurbinectedin safe for individuals who had already tried other treatments. Another study examined data from 554 patients with advanced solid tumors and confirmed that the treatment's side effects were manageable. Overall, lurbinectedin appears safe for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lurbinectedin is unique because it targets the DNA of cancer cells in a way that disrupts their ability to replicate, which is different from traditional chemotherapy approaches. Researchers are excited about this treatment for Ewing sarcoma because it offers a novel mechanism of action by binding to the DNA minor groove, potentially leading to more effective targeting of cancer cells with fewer side effects. Unlike standard treatments like chemotherapy and radiation, lurbinectedin's specific action on DNA may result in improved outcomes for patients with recurrent or refractory forms of the disease.

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

Research shows that lurbinectedin attacks the DNA of cancer cells, helping to stop their growth. In studies with patients who have various solid tumors, lurbinectedin has shown promising results. Some patients experienced tumor reduction, suggesting the treatment's effectiveness. This trial specifically examines lurbinectedin's impact on Ewing sarcoma. Early reports suggest potential benefits for this condition, but more information is needed to confirm these effects. Researchers continue to study the treatment to better understand its impact on Ewing sarcoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Jazz Study Director

Principal Investigator

Jazz Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for young individuals aged 2 to 30 with relapsed/refractory Ewing Sarcoma. They must have a solid tumor diagnosis, acceptable organ function, and performance status. Participants need adequate bone marrow, liver, kidney, and heart functions and weigh over 15 kg. Males must agree to contraception rules; females cannot be pregnant or breastfeeding and must use contraception.

Inclusion Criteria

I weigh at least 15 kilograms.

I have a confirmed solid tumor.

I am following the required birth control measures.

Exclusion Criteria

I do not have any major illnesses that could worsen my health significantly.

Participant with corrected QT interval (QTc) prolongation

I have lasting side effects from previous treatments, but not including certain conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Selection

Pediatric participants with previously treated solid tumors receive lurbinectedin at 5 dose levels to determine the RP2D, followed by a safety expansion cohort.

Approximately 12 months

Phase 1: RP2D

Participants with recurrent/refractory Ewing sarcoma receive lurbinectedin at the RP2D to assess safety and efficacy signals.

Approximately 6 months

Phase 2

Further assessment of safety and efficacy of lurbinectedin monotherapy in participants with recurrent/refractory Ewing sarcoma.

Approximately 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lurbinectedin

Trial Overview The study tests Lurbinectedin monotherapy in two phases: Phase 1 determines the safe dosage and observes how the body processes the drug; Phase 2 evaluates its effectiveness specifically in pediatric/young adult patients with recurrent Ewing sarcoma after previous treatments.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 1 Intervention

If a signal of efficacy is observed in Phase 1 Part 2, additional participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma will be enrolled. Phase 2 will further assess the safety and efficacy of lurbinectedin monotherapy.

Group II: Phase 1 Part 2: RP2D Experimental Treatment 1 Intervention

Participants aged ≥ 2 to ≤ 30 years with recurrent/refractory Ewing sarcoma at the RP2D to assess safety and efficacy signals.

Group III: Phase 1 Part 1: Dose Selection Experimental Treatment 1 Intervention

Pediatric participants ≥ 2 to \< 18 years of age with previously treated solid tumors of any histology at 5 dose levels to determine the RP2D, followed by a safety expansion cohort. Participants aged ≥ 6 to \< 18 years will be enrolled at the starting dose of 3.2 mg/m\^2 lurbinectedin. After the drug is deemed safe based safety and PK data from the older participants, participants aged ≥ 2 to \< 6 years are enrolled at the same starting dose. After this, the study opens to all participants (aged ≥ 2 to \< 18 years) for all dose levels. Upon completion of the cohort at all dose levels, participants may be eligible to enroll in a safety expansion cohort.

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?

Jazz Pharmaceuticals

Lead 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

Published Research Related to This Trial

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]

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT02454972

NCT02454972 | Clinical Trial of Lurbinectedin (PM01183) ... Multicenter, open-label, exploratory, phase II clinical trial to evaluate the efficacy and safety of PM01183 in previously treated patients with advanced solid ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05042934?id=%22NCT01858168%22OR%22NCT01864109%22OR%22NCT02044120%22OR%22NCT02511132%22OR%22NCT03416517%22OR%22NCT03495921%22OR%22NCT04067115%22OR%22NCT05042934%22&rank=1

Study Details | Lurbinectedin With or Without Irinotecan in ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. fda.gov fda.gov/media/106153/download

Lurbinectedin (PM01183) for the Treatment of Ewing ... Once safety information for this subgroups is available to continue including pediatric population subgroups: infants and toddlers (28 days ...

8. 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 ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0959804923003611

Pooled Safety Analysis of Single-Agent Lurbinectedin in ... Lurbinectedin has a manageable safety profile in second-line treatment of SCLC. Safety of approved dose was assessed in 554 patients with advanced solid ...