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NCT Number: NCT04067115

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

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.

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Key information

Conditions

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

Age range

6 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Children's Hospital of Los Angeles, Los Angeles, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Trabectedin 1 MG [Yondelis]

Drug

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

Irinotecan

Drug

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

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.

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.

Other names: 18F-FLT Imaging

Primary outcomes

  1. Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan

    Time frame: up to 36 months

    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).

  2. Phase I Tumor response rate

    Time frame: up to 36 months

    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

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

    Time frame: up to 36 months

    Tumor objective response rate (ORR) assessed by RECIST v1.1.

Secondary outcomes

  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.

    Time frame: up to 36 months

    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.

  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

    Time frame: up to 36 months

    18F-FLT PET avidity of Ewing sarcoma tumors.

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

    Time frame: up to 36 months

    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

  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.

    Time frame: up to 36 months

    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.

  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.

    Time frame: up to 36 months

    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.

Other outcomes

  1. Progression free survival

    Time frame: up to 5 years

    The time from starting treatment until disease progression

  2. 6- month Progression free survival

    Time frame: up to 36 months

    To determine the rate of disease progression at 6 months after starting treatment

  3. Duration of Response

    Time frame: up to 5 years

    The time from tumor response to disease progression

Sponsors and collaborators

Lead sponsor

Sarcoma Alliance for Research through Collaboration

Other

Collaborators

  • Janssen Scientific Affairs, LLC
  • National Cancer Institute (NCI)
  • National Institutes of Health (NIH)

Registry information

Official study 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

Acronym: U01CA236220

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
Aug 26, 2019
Registry last updated
Dec 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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