Lurbinectedin for Ewing Sarcoma

(EMERGE 101 Trial)

Recruiting at 14 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Jazz Pharmaceuticals

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

Disqualifiers: CNS metastases, Uncontrolled illness, HIV, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called lurbinectedin in children and young adults who have already been treated for solid tumors or have a type of cancer called Ewing sarcoma that has come back or didn't respond to other treatments. The medication aims to stop cancer cells from growing and spreading. The study will check if the treatment is safe and effective.

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.

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 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

Jazz Study Director

Principal Investigator

Jazz Pharmaceuticals

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Lurbinectedin (Alkylating agent)

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.

Participant Groups

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.

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

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]

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]

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]

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

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

5. 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]