What is the mechanism of action of this treatment?

Common treatments for Ewing Sarcoma include chemotherapy, radiation therapy, and surgery. Chemotherapy agents like doxorubicin work by intercalating DNA and inhibiting topoisomerase II, leading to DNA damage and apoptosis. Radiation therapy damages the DNA of cancer cells, causing cell death. Surgery aims to remove the tumor entirely. Lurbinectedin, similar to other transcription inhibitors, disrupts the transcription process, leading to apoptosis. These mechanisms are crucial as they target the rapid proliferation and survival pathways of Ewing Sarcoma cells, aiming to reduce tumor burden and improve patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for Ewing Sarcoma, including chemotherapy agents like doxorubicin, cyclophosphamide, and vincristine, often cause side effects such as myelosuppression, nausea, vomiting, alopecia, mucositis, and cardiotoxicity. Newer agents like Lurbinectedin, which inhibit transcription and induce apoptosis, may also lead to side effects such as fatigue, neutropenia, thrombocytopenia, and elevated liver enzymes.

What prior FDA approvals exist?

The FDA has approved several treatments for Ewing Sarcoma, primarily focusing on chemotherapy regimens. Commonly used drugs include vincristine, dactinomycin, and ifosfamide (VIDE), often combined with other agents like busulfan and melphalan for high-dose chemotherapy followed by autologous hematopoietic cell transplantation. While Lurbinectedin, which inhibits transcription leading to apoptosis, is being studied in clinical trials, it has not yet received FDA approval specifically for Ewing Sarcoma. Current treatments aim to manage the disease through a combination of systemic chemotherapy and local control measures such as surgery and radiation therapy.

What other types of research exist?

Promising novel alternatives to Lurbinectedin for Ewing Sarcoma patients include: 1) Trabectedin, which has shown efficacy in advanced translocation-related sarcomas. 2) Pazopanib, a multikinase angiogenesis inhibitor, which has demonstrated activity in various soft tissue sarcomas. These alternatives have been evaluated in clinical trials and may offer therapeutic benefits for Ewing Sarcoma patients.

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Alkylating agent

Lurbinectedin for Ewing Sarcoma (EMERGE 101 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Jazz Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up post-baseline (day 1) up to approximately 30 months.

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not explicitly listed here, potential side effects of Lurbinectedin may include fatigue, nausea, hair loss (alopecia), decreased appetite, constipation or diarrhea as common chemotherapy-related reactions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ post-baseline (day 1) up to approximately 30 months.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~post-baseline (day 1) up to approximately 30 months.

This trial's timeline: 3 weeks for screening, Varies for treatment, and post-baseline (day 1) up to approximately 30 months. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase 2Experimental Treatment1 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: RP2DExperimental Treatment1 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 SelectionExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lurbinectedin

2022

Completed Phase 3

~780

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Ewing Sarcoma include chemotherapy, radiation therapy, and surgery. Chemotherapy agents like doxorubicin work by intercalating DNA and inhibiting topoisomerase II, leading to DNA damage and apoptosis. Radiation therapy damages the DNA of cancer cells, causing cell death. Surgery aims to remove the tumor entirely. Lurbinectedin, similar to other transcription inhibitors, disrupts the transcription process, leading to apoptosis. These mechanisms are crucial as they target the rapid proliferation and survival pathways of Ewing Sarcoma cells, aiming to reduce tumor burden and improve patient outcomes.

The Protective Effect of Luteolin in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.Trabectedin modulates the senescence-associated secretory phenotype and promotes cell death in senescent tumor cells by targeting NF-κB.Doxorubicin Inhibits Proliferation of Osteosarcoma Cells Through Upregulation of the Notch Signaling Pathway.