SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients
- Conditions
- Ewing Sarcoma
- Interventions
- Diagnostic Test: tumor biopsyOther: 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging
- Registration Number
- NCT04067115
- Brief 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.
Phase I was completed on 11/16/2022. Phase II is actively recruiting.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Trabectedin and Irinotecan tumor biopsy 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. Trabectedin and Irinotecan 3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging 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. Trabectedin and Irinotecan Trabectedin 1 MG [Yondelis] 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. Trabectedin and Irinotecan 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.
- Primary Outcome Measures
Name Time Method Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan 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).Phase I Tumor response rate 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
Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan up to 36 months Tumor objective response rate (ORR) assessed by RECIST v1.1.
- Secondary Outcome Measures
Name Time Method 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. 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.
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 up to 36 months 18F-FLT PET avidity of Ewing sarcoma tumors.
Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan 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
Trial Locations
- Locations (6)
Boston Children's Hospital / Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
National Cancer Institute
🇺🇸Bethesda, Maryland, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States