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

NCT ID: NCT04067115

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-05

Study Completion Date

2025-04-24

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Ewing Sarcoma

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Trabectedin 1 MG [Yondelis]

Intervention Type DRUG

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

Irinotecan

Intervention Type DRUG

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

tumor biopsy

Intervention Type 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.

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

Intervention Type OTHER

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

Interventions

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Trabectedin 1 MG [Yondelis]

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

Intervention Type DRUG

Irinotecan

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

Intervention Type DRUG

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.

Intervention Type DIAGNOSTIC_TEST

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.

Intervention Type OTHER

Other Intervention Names

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18F-FLT Imaging

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Sarcoma Alliance for Research through Collaboration

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patrick Grohar, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

John Glod, MD/PhD

Role: STUDY_DIRECTOR

National Cancer Institute (NCI)

Locations

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Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status

National Cancer Institute

Bethesda, Maryland, United States

Site Status

Boston Children's Hospital / Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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U01CA236220

Identifier Type: NIH

Identifier Source: secondary_id

View Link

SARC037

Identifier Type: -

Identifier Source: org_study_id