Clinical Trials /

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

NCT04067115

Description:

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.

Related Conditions:
  • Ewing Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04067115

Trial Eligibility

Document

Title

  • Brief Title: SARC037: A Phase I Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients
  • Official Title: SARC037: A Phase I 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

Clinical Trial IDs

  • ORG STUDY ID: SARC037
  • SECONDARY ID: U01CA236220
  • NCT ID: NCT04067115

Conditions

  • Ewing Sarcoma

Interventions

DrugSynonymsArms
Trabectedin 1 MG [Yondelis]Trabectedin and Irinotecan
IrinotecanTrabectedin and Irinotecan

Purpose

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

      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.

Trial Arms

NameTypeDescriptionInterventions
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.
  • Trabectedin 1 MG [Yondelis]
  • Irinotecan

Eligibility Criteria

        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
Maximum Eligible Age:99 Years
Minimum Eligible Age:10 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan
Time Frame:up to 36 months
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Tumor response rate
Time Frame:up to 36 months
Safety Issue:
Description:The percentage of patients whose tumor shrinks or disappears after treatment (per RECIST 1.1)
Measure:18F-FLT PET avidity of Ewing sarcoma tumors.
Time Frame:up to 36 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sarcoma Alliance for Research through Collaboration

Last Updated

May 7, 2021