search
Back to results

SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients (U01CA236220)

Primary Purpose

Ewing Sarcoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Trabectedin 1 MG [Yondelis]
Irinotecan
tumor biopsy
3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging
Sponsored by
Sarcoma Alliance for Research through Collaboration
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing Sarcoma

Eligibility Criteria

6 Years - 99 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital of Los AngelesRecruiting
  • National Cancer InstituteRecruiting
  • Boston Children's Hospital / Dana Farber Cancer InstituteRecruiting
  • University of MichiganRecruiting
  • Children's Hospital of PhiladelphiaRecruiting
  • University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Trabectedin and Irinotecan

Arm Description

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.

Outcomes

Primary Outcome Measures

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).
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
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.

Secondary Outcome Measures

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.
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.
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
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.
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.

Full Information

First Posted
August 21, 2019
Last Updated
September 15, 2023
Sponsor
Sarcoma Alliance for Research through Collaboration
Collaborators
Janssen Scientific Affairs, LLC, National Institutes of Health (NIH), National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04067115
Brief Title
SARC037: A Phase I/II Study to Evaluate the Safety of Trabectedin in Combination With Irinotecan in Ewing Sarcoma Patients
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 5, 2021 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarcoma Alliance for Research through Collaboration
Collaborators
Janssen Scientific Affairs, LLC, National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ewing Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Trabectedin and Irinotecan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Trabectedin 1 MG [Yondelis]
Intervention Description
Patients with Ewing sarcoma will be administered trabectedin intravenously. Cycles are 21 days.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Patients with Ewing sarcoma will be administered inirotecan intravenously. Cycles are 21 days.
Intervention Type
Diagnostic Test
Intervention Name(s)
tumor biopsy
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
3'-Deoxy-3'-18F Fluorothymidine (18F-FLT) Imaging
Other Intervention Name(s)
18F-FLT Imaging
Intervention Description
Some patients will receive PET scans with the use of 18F-FLT, a radioactive tracer, performed at the National Institute of Health.
Primary Outcome Measure Information:
Title
Phase I The recommended dose (RD) of trabectedin administered in combination with low dose irinotecan
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).
Time Frame
up to 36 months
Title
Phase I Tumor response rate
Description
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
Time Frame
up to 36 months
Title
Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan
Description
Tumor objective response rate (ORR) assessed by RECIST v1.1.
Time Frame
up to 36 months
Secondary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
up to 36 months
Title
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
Description
18F-FLT PET avidity of Ewing sarcoma tumors.
Time Frame
up to 36 months
Title
Phase 2 To determine anti-tumor activity of the combination trabectedin and low-dose irinotecan
Description
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
Time Frame
up to 36 months
Title
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.
Description
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.
Time Frame
up to 36 months
Title
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.
Description
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.
Time Frame
up to 36 months
Other Pre-specified Outcome Measures:
Title
Progression free survival
Description
The time from starting treatment until disease progression
Time Frame
up to 5 years
Title
6- month Progression free survival
Description
To determine the rate of disease progression at 6 months after starting treatment
Time Frame
up to 36 months
Title
Duration of Response
Description
The time from tumor response to disease progression
Time Frame
up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
SARC
Phone
7349307600
Email
sarc@sarctrials.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Grohar, MD/PhD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Glod, MD/PhD
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abe Levi, CRSO
Phone
323-361-6686
First Name & Middle Initial & Last Name & Degree
Leo Mascarenhas, MD
Facility Name
National Cancer Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Glod, MD
Facility Name
Boston Children's Hospital / Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Dubois, MD
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rashmi Chugh, MD
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Grohar, MD/PhD
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tara Perloff
Email
tara.perloff@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Mark Diamond, MD

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs