NCT05042934

Lurbinectedin With or Without Irinotecan in Treating Patients With Relapsed or High Risk Metastatic Ewing Sarcoma

Phase 1B/2 Study of Lurbinectedin With or Without Irinotecan for Patients With Relapsed or High Risk Chemotherapy-Naive Ewing Sarcoma

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib/II trial studies best dose and side effects of lurbinectedin and how well it works with or without irinotecan in treating patients with Ewing sarcoma that has come back (relapsed) or is high risk and has spread to other places in the body (metastatic). Lurbinectedin may decrease chemicals in the body related to Ewing sarcoma, and reducing these chemicals may make the tumor cells more sensitive to irinotecan. Chemotherapy drugs, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving lurbinectedin with or without irinotecan may work better in treating patients with Ewing sarcoma.

Detailed description

PRIMARY OBJECTIVES: I. To determine the time course of nuclear receptor subfamily 0 group B member 1 (NR0B1) suppression, Werner syndrome RecQ like helicase (WRN) suppression, and S-phase blockade after lurbinectedin (PM01183) administration in patients with Ewing sarcoma and Ewing's Sarcoma-Friend leukemia integration 1 transcription factor (EWS-FLI1) translocation. (Phase IB) II. To determine whether similar NR0B1 suppression, and S-phase blockade after lurbinectedin (PM01183) administration is seen in patients with Ewing sarcoma other EWSR1 translocations. (Phase IB) III. To determine the recommended dose (RD) of lurbinectedin (PM01183) in combination with irinotecan every 3 weeks for patients with relapsed Ewing sarcoma. (Phase IB) IV. To assess the activity of lurbinectedin in combination with low-dose irinotecan in patients with relapsed Ewing sarcoma. (Phase II) V. To assess if the suppression of NR0B1is extended after combining irinotecan with lurbinectedin. (Phase II) VI. To assess the histological characteristics of patients with prolonged stable disease to determine if they are true responders. (Phase II) OUTLINE: This is a phase Ib, dose-escalation study of lurbinectedin, followed by a phase II study. Patients receive lurbinectedin intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo fine-needle aspiration on days 2-6 of cycle 1. Beginning in cycle 2, if the biopsy shows suppression of NR0B1, then patients receive irinotecan IV over 1 hour on the day of maximum NR0B1 suppression on cycle 2. If the duration of NR0B1 suppression from lurbinectedin alone exceeds 48 hours, or if the duration of NR0B1 suppression from lurbinectedin and irinotecan exceeds 48 hours and is longer than that seen with lurbinectedin alone, then patients may receive a second dose of irinotecan during the extended period of NR0B1 suppression. After completion of study treatment, patients are followed up at 30 days, every 2 months for 6 months, and then every 3 months for at least 2 years.

Conditions

• Metastatic Ewing Sarcoma
• Recurrent Ewing Sarcoma

Interventions

Type	Name	Description
PROCEDURE	Fine-Needle Aspiration	Undergo fine-needle aspiration
DRUG	Irinotecan	Given IV
DRUG	Irinotecan Hydrochloride	Given IV
DRUG	Lurbinectedin	Given IV

Timeline

• Start date: 2021-09-15
• Primary completion: 2022-08-30
• Completion: 2022-08-30
• First posted: 2021-09-13
• Last updated: 2022-02-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study