Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2025-12-25 @ 2:32 AM
NCT ID:
NCT05042934
Brief 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.
Study:
NCT05042934
Study Brief:
Protocol Section:
NCT05042934