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

Ewing Sarcoma Clinical Trial

— U01CA236220  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04067115
• Other study ID #: SARC037
• Secondary ID: U01CA236220
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 5, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: September 2023
• Source: Sarcoma Alliance for Research through Collaboration
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Phase I was completed on 11/16/2022. Phase II is actively recruiting.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Ewing Sarcoma
• Sarcoma
• Sarcoma, Ewing

Intervention

Drug:
• Trabectedin 1 MG [Yondelis]
Patients with Ewing sarcoma will be administered trabectedin intravenously. Cycles are 21 days.
• Irinotecan
Patients with Ewing sarcoma will be administered inirotecan intravenously. Cycles are 21 days.

Diagnostic Test:
• tumor biopsy
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.

Other:
• 3'-Deoxy-3'-18F Fluorothymidine (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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	National Cancer Institute	Bethesda	Maryland
United States	Boston Children's Hospital / Dana Farber Cancer Institute	Boston	Massachusetts
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
Sarcoma Alliance for Research through Collaboration	Janssen Scientific Affairs, LLC, National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression free survival	The time from starting treatment until disease progression	up to 5 years
Other	6- month Progression free survival	To determine the rate of disease progression at 6 months after starting treatment	up to 36 months
Other	Duration of Response	The time from tumor response to disease progression	up to 5 years
Primary	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).	up to 36 months
Primary	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	up to 36 months
Primary	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.	up to 36 months
Secondary	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.	up to 36 months
Secondary	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.	up to 36 months
Secondary	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	up to 36 months
Secondary	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.	up to 36 months
Secondary	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.	up to 36 months