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

NCT04067115 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: SARC037U01CA236220
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Ewing Sarcoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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.

  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

  up to 36 months

• Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose 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.

  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.

  up to 36 months

Other Outcomes (3)

• Progression free survival

  up to 5 years

• 6- month Progression free survival

  up to 36 months

• Duration of Response

  up to 5 years

Study Arms (1)

Trabectedin and Irinotecan

EXPERIMENTAL

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]; Drug: Irinotecan; Diagnostic Test: tumor biopsy; Other: 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging

Interventions

Irinotecan DRUG

Patients with Ewing sarcoma will be administered inirotecan intravenously. Cycles are 21 days.

Trabectedin and Irinotecan

tumor biopsy DIAGNOSTIC_TEST

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.

Trabectedin and Irinotecan

3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging OTHER

Some patients will receive PET scans with the use of 18F-FLT, a radioactive tracer, performed at the National Institute of Health.

Also known as: 18F-FLT Imaging

Trabectedin and Irinotecan

Trabectedin 1 MG [Yondelis] DRUG

Patients with Ewing sarcoma will be administered trabectedin intravenously. Cycles are 21 days.

Trabectedin and Irinotecan

Eligibility Criteria

• Age: 6 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• Janssen Scientific Affairs, LLC: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Boston Children's Hospital / Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48106, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19105, United States

Location

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

Trabectedin; Irinotecan; alovudine; X-Rays

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Patrick Grohar, MD/PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• John Glod, MD/PhD

  National Cancer Institute (NCI)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This phase I study will follow a standard 3+3 design and the Phase II study will be a single-arm, mini-max Simon two-stage design.

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 26, 2019
• Study Start: January 5, 2021
• Primary Completion: April 24, 2025
• Study Completion: April 24, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (6)