SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients (U01CA236220)

SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin Administered as a 1-Hour Infusion in Ewing Sarcoma Patients in Combination With Low Dose Irinotecan and 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging

This study evaluates the trabectedin and irinotecan in the treatment of Ewings sarcoma, with a EWS-FLI1 mutation. Patients will also receive an infusion of 18F-FLT in combination with a Positron Emission Tomography (PET) scan to help evaluate the effect of treatment.

Study Overview

• Status: Completed
• Conditions: Ewing Sarcoma
• Intervention / Treatment: Drug: Trabectedin 1 MG [Yondelis]; Drug: Irinotecan; Diagnostic test: tumor biopsy; Other: 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging

Detailed Description

Trabectedin and Irinotecan may inhibit the activity of this Ewing sarcoma mutation. Trabectedin may suppress the proliferation of the gene involved in DNA damage response. It blocks EWS-FLI1 by inactivating the fusion protein and silences the target genes.

Irinotecan also suppresses the genes regulating the tumor cells, generating DNA damage. Together, these drugs work in combination to suppress the gene regulating the tumor cells. This combination may suppress the activity of the tumor regulating genes, disrupting the activity of the genes. The infusion of 18F-FLT in combination with a Positron Emission Tomography (PET) scan will demonstrate whether the target cells have been suppressed.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston Children's Hospital / Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19105
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• diagnosis of relapsed and refractory Ewing sarcoma with EWS-FLI1 fusion type for which there is no known therapy proving to prolong survival
• measurable disease
• ECOG Performance Status of 0-2 or Lansky of 50
• adequate organ function
• written, voluntary consent
• willing to undergo tumor biopsy
• negative hepatitis infection

Exclusion Criteria:

• prior therapy with trabectedin or lurbinectedin
• known history of hypersensitivity to irinotecan or topotecan or their excipients.
• known brain metastases
• known bleeding diathesis
• pregnant or breastfeeding
• currently receiving other investigational drugs or anticancer agents
• clinically significant unrelated illness or uncontrolled infection
• unable to comply with the safety monitoring requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Trabectedin and Irinotecan; Trabectedin will be delivered by infusion on day 1 followed by 2 doses on irinotecan delivered by infusion for one hour on day 2 and day 4 of 21 day cycles. Some patients will receive an 18F-FLT Imaging scan prior to the first administration of trabectedin and once after administration of trabectedin.

Drug: Trabectedin 1 MG [Yondelis]; Patients with Ewing sarcoma will be administered trabectedin intravenously. Cycles are 21 days.; Drug: Irinotecan; Patients with Ewing sarcoma will be administered inirotecan intravenously. Cycles are 21 days.; Diagnostic test: tumor biopsy; Tumor tissue samples will be collected collected at two timepoints. The first biopsy will be prior to treatment. If a biopsy is not possible archival tissue may be submitted. A second tumor biopsy will be taken fro consenting patients when possible after the first administration of Trabectedin to evaluate the effect on the tumor cells.; Other: 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging; Some patients will receive PET scans with the use of 18F-FLT, a radioactive tracer, performed at the National Institute of Health.; Other Names: 18F-FLT Imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan	The recommended dose will be established by enrolling patients at the lowest dose and observing them for dose limiting toxicity. Dose limiting toxicity describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. The maximum tolerated dose is the highest dose of a drug or treatment that does not cause unacceptable side effects. If 0 of the first 3 subjects experience DLT, the study will proceed to the next dose level. If 1 subject experiences a DLT, that dose level cohort will be expanded to 6 total subjects. If no additional subjects experience DLTs at that dose level cohort, the study will proceed to enroll the next dose level cohort. If ≥ 2 of 6 subjects experience DLT, then that dose level is the recommended dose of trabectedin (RD). The study will proceed to the same process for the irinotecan escalation. If 2 or all 3 subjects experience DLT, that dose level is the recommended dose of trabectedin (RD).	up to 36 months
Phase I Tumor response rate	The anti-tumor activity of the combination of trabectedin and low-dose irinotecan as measured by the tumor objective response rate (ORR) assessed by RECIST v1.1	up to 36 months
Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan	Tumor objective response rate (ORR) assessed by RECIST v1.1.	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I/Phase 2 Tumor response rate, progression-free survival (PFS), duration of response, and 6-month PFS rate of patients with ES treated with trabectedin and irinotecan.	The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1), progression-free survival (PFS) of patients with ES treated with trabectedin and irinotecan.	up to 36 months
Phase I monitor the avidity of Ewing sarcoma tumors of EWS-FLI1 12-24 hours after trabectedin administration and before irinotecan is administered and before 18F-FLT PET scans	18F-FLT PET avidity of Ewing sarcoma tumors.	up to 36 months
Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan	The anti-tumor activity of the combination of trabectedin and low-dose irinotecan as measured by the tumor objective response rate (ORR) assessed by RECIST v1.1	up to 36 months
Phase I/Phase 2 Tumor response rate, progression-free survival (PFS), duration of response, and 6-month PFS rate of patients with ES treated with trabectedin and irinotecan.	The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1) duration of response of patients with ES treated with trabectedin and irinotecan.	up to 36 months
Phase I/Phase 2 Tumor response rate, progression-free survival (PFS), duration of response, and 6-month PFS rate of patients with ES treated with trabectedin and irinotecan.	The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1) duration of 6-month PFS rate ES treated with trabectedin and irinotecan.	up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	The time from starting treatment until disease progression	up to 5 years
6- month Progression free survival	To determine the rate of disease progression at 6 months after starting treatment	up to 36 months
Duration of Response	The time from tumor response to disease progression	up to 5 years

Collaborators and Investigators

• Sponsor: Sarcoma Alliance for Research through Collaboration
• Collaborators: National Cancer Institute (NCI); Janssen Scientific Affairs, LLC; National Institutes of Health (NIH)
• Investigators: Principal Investigator: Patrick Grohar, MD/PhD, Children's Hospital of Philadelphia; Study Director: John Glod, MD/PhD, National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): April 24, 2025
• Study Completion (Actual): April 24, 2025

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma, Ewing; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Physical Phenomena; Camptothecin; Alkaloids; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Dioxoles; Tetrahydroisoquinolines; Isoquinolines; Irinotecan; Trabectedin; X-Rays; alovudine
• Other Study ID Numbers: SARC037; U01CA236220 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No