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

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.

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.

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