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Ewing SarcomaPhase 1/2U01CA236220NCT04067115

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

A Phase 1/2 study testing Trabectedin 1 MG [Yondelis], Irinotecan and tumor biopsy in people with Ewing Sarcoma, run by Sarcoma Alliance for Research through Collaboration at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 to 99 years
Conditions the study is for
Ewing Sarcoma
What is being tested?
Trabectedin 1 MG [Yondelis], Irinotecan and tumor biopsy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
6 sitesUnited States
Study dates
5 Jan 2021to 24 Apr 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 99 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • University of Michigan

    Ann Arbor, Michigan, 48106

  • National Cancer Institute

    Bethesda, Maryland, 20892

  • Boston Children's Hospital / Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19105

Other trials in United States

About this study

Official title: 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.

Read the 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.

Conditions
Ewing Sarcoma
Being tested
Trabectedin 1 MG [Yondelis], Irinotecan, tumor biopsy, 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging
Medical subject headings
Sarcoma, Ewing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trabectedin 1 MG [Yondelis]Drug

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

  • IrinotecanDrug

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

  • tumor biopsyDiagnostic 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) ImagingOther

    Also called 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.

Study groups in NCT04067115
Study groupRoleWhat they receive
Trabectedin and IrinotecanExperimentalTrabectedin 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.
Receives: Drug: Trabectedin 1 MG [Yondelis]; Drug: Irinotecan; Diagnostic Test: tumor biopsy; Other: 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: up to 36 months

  2. 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

    Measured: up to 36 months

  3. 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.

    Measured: up to 36 months

Secondary outcomes (5)

  1. 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.

    Measured: up to 36 months

  2. 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.

    Measured: up to 36 months

  3. 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

    Measured: up to 36 months

  4. 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.

    Measured: up to 36 months

  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.

    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.

    Measured: up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2019
  2. Study start5 Jan 2021
  3. Primary completion24 Apr 2025
  4. Study completion24 Apr 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04067115
Sponsor's protocol ID
SARC037
Other IDs
U01CA236220
Acronym
U01CA236220
Status last verified
Dec 2025
First submitted
21 Aug 2019
Last updated
17 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Grohar PJ, Heise R, Wedekind MF, Ballman K, Mascarenhas L, DuBois SG, Maki RG, Boguslawski EA, Gedminas JM, Wilson ER, Thomas E, Segers B, Surrey LF, Ricker C, Klega K, Navid F, Lam GY, The S, Kaufman R, Roberts RD, Hayashi M, Mena E, Overman L, Peer C, Schmidt K, Diamond MS, Figg WD, Bagatell R, Liza Lindenberg M, Choyke PL, Crompton BD, Widemann BC, Glod JW, Laetsch TW, Reinke DK, Chugh R. Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial. Nat Med. 2026 Jun;32(6):2227-2237. doi: 10.1038/s41591-026-04340-7. Epub 2026 Apr 16.

    PubMed 41991689

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trabectedin 1 MG [Yondelis], Irinotecan and tumor biopsy in people with Ewing Sarcoma, run by Sarcoma Alliance for Research through Collaboration at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan (time frame: up to 36 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04067115, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.

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