Clinical trial NCT04067115: SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ewing Sarcoma
Lead sponsor: Sarcoma Alliance for Research through Collaboration
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2019-08-26
Enrollment: 37
Sex: ALL
Minimum age (years): 6
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: This phase I study will follow a standard 3+3 design and the Phase II study will be a single-arm, mini-max Simon two-stage design.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan
timeFrame: up to 36 months
measure: Phase I Tumor response rate
timeFrame: up to 36 months
measure: Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan
timeFrame: up to 36 months
Secondary outcomes:
measure: 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.
timeFrame: up to 36 months
measure: 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
timeFrame: up to 36 months
measure: Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan
timeFrame: up to 36 months
measure: 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.
timeFrame: up to 36 months
measure: 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.
timeFrame: up to 36 months
Other outcomes:
measure: Progression free survival
timeFrame: up to 5 years
measure: 6- month Progression free survival
timeFrame: up to 36 months
measure: Duration of Response
timeFrame: up to 5 years
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital / Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Patrick Grohar, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute (NCI)
name: John Glod, MD/PhD
role: STUDY_DIRECTOR
References: