Liquid Biopsy in Ewing Sarcoma and Osteosarcoma as a Prognostic And Response Diagnostic: LEOPARD

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT06068075

Collaborator

Alex's Lemonade Stand Foundation (Industry), Conquer Cancer Foundation (Other), Harvard University (Other), Sam Day Foundation (Other)

340

Enrollment

Locations

Arms

91.8

Anticipated Duration (Months)

22.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective multicenter biomarker study evaluating the prognostic impact of ctDNA detection at diagnosis in patients with Ewing sarcoma or osteosarcoma.

Condition or Disease	Intervention/Treatment	Phase
Ewing Sarcoma Ewing Sarcoma of Bone Ewing Sarcoma of Soft Tissue Peripheral Primitive Neuroectodermal Tumor Peripheral Primitive Neuroectodermal Tumor of Bone Peripheral Primitive Neuroectodermal Tumor of Soft Tissue High-grade Osteosarcoma	Other: FoundationOne Liquid CDx	N/A

Detailed Description

The purpose of this study is to evaluate whether ctDNA in the blood can provide information about the chances of Ewing sarcoma or osteosarcoma coming back after treatment. This research study is evaluating a new advanced laboratory test to detect small pieces of tumor genes in the peripheral blood known as circulating tumor DNA (ctDNA).

Part A : During this part of the research study (Part A) participants will be asked to provide blood samples at pre-defined times. These blood samples may help find specific genetic alterations commonly seen in Ewing sarcoma or osteosarcoma that may allow investigators to learn more about the uses of ctDNA. The results of the ctDNA analysis will not be returned to participants.

Approximately 90 patients will take part in this study across multiple centers.

Part B: This research study is evaluating new advanced laboratory tests to detect small pieces of tumor genes in the peripheral blood known as circulating tumor DNA (ctDNA). Part B of the research study, which focuses on ctDNA tests that can be returned to providers and patients with Ewing sarcoma. This part of the study will allow comparison of commercial ctDNA testing from Foundation Medicine to our research testing. It is expected that about 60 people with Ewing sarcoma will take part in Part B of this research study.

The sponsor of this protocol is Dana-Farber Cancer Institute and is providing funding for the study. Additional funding for this study is provided by the Conquer Cancer Foundation of the American Society of Clinical Oncology, Alex's Lemonade Stand Foundation, Boston Children's Hospital Office of Faculty Development, the Friends of Dana-Farber Cancer Institute, The Harvard Catalyst Program, and the Spada Pediatric Sarcoma Foundation

Study Design

Study Type:

Interventional

Anticipated Enrollment :

340 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Liquid Biopsy in Ewing Sarcoma and Osteosarcoma as a Prognostic And Response Diagnostic: The LEOPARD Study

Actual Study Start Date :

May 8, 2018

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: REG EWING or OSTEO: ctDNA EVALUATION This study involves collection of blood samples at pre-specified time points as well as collection of information about this disease. For each timepoint, submit two tubes of blood (17 mL total or a little more than 3 teaspoons) per standard ctDNA workflow
Experimental: EWING ctDNA RETURN OF RESULTS This study involves collection of blood samples at pre-specified time points as well as collection of information about this disease. For each timepoint, submit two tubes of blood (17 mL total or a little more than 3 teaspoons) to a commercial testing laboratory called Foundation Medicine and one tube of blood (10 mL or 2 teaspoons) to standard ctDNA workflow	Other: FoundationOne Liquid CDx a FoundationOne liquid biopsy test kit will be sent to the laboratory of the subject's treating center, in addition to the paired cell stabilizing tube from the primary center Other Names: Liquid Biopsy

Arm

Intervention/Treatment

No Intervention: REG EWING or OSTEO: ctDNA EVALUATION

This study involves collection of blood samples at pre-specified time points as well as collection of information about this disease. For each timepoint, submit two tubes of blood (17 mL total or a little more than 3 teaspoons) per standard ctDNA workflow

Experimental: EWING ctDNA RETURN OF RESULTS

Other: FoundationOne Liquid CDx

a FoundationOne liquid biopsy test kit will be sent to the laboratory of the subject's treating center, in addition to the paired cell stabilizing tube from the primary center

Other Names:

Liquid Biopsy

Outcome Measures

Primary Outcome Measures

Event-free survival rate [2 years]
Proportion of patient without an event by baseline detection of ctDNA

Secondary Outcome Measures

Event-free survival rate [2 years]
Proportion of patient without an event by ctDNA burden at baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

For Part A, subjects must meet all of the following eligibility criteria.
Age: ≥ 12 months of age at time of study enrollment to 50 years of age
Diagnosis: Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed, localized or regionally disseminated Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) of bone or soft tissue or; Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed, non-pelvic, localized or regionally disseminated high-grade osteosarcoma. NOTE: Staging will be assessed according to standard of care at the treating center.
Prior Therapy:
Patients should have only previously had a biopsy, and not had prior attempt at tumor resection.
Not yet started chemotherapy or radiation therapy OR patient has started chemotherapy or radiation therapy, but an appropriate pre-treatment baseline sample was collected and processed for ctDNA under a local banking study in DFCI Pediatrics and is available to use for this study.
Planned to receive chemotherapy as follows:

-- VDC/IE as per COG protocols AEWS0031, AEWS1031 or AEWS1221 (for patients with Ewing sarcoma or PNET); or MAP as per COG protocol AOST0331 (for patients with osteosarcoma).

For Part B subjects must meet all of the following eligibility criteria.
Age: ≥ 12 months of age at time of study enrollment
Diagnosis: Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) of bone or soft tissue
Prior Therapy:
Patients should have had only frontline therapy as per institutional standard, and maintenance therapy if given (no relapse therapy).
If frontline systemic therapy already completed (not including maintenance or metastatic site radiation), therapy completed within 6 months of enrollment to Part B.
Subjects must have a willing physician provider supporting their participation in Part B.
For Part B, providers are eligible to receive the provider survey if they are listed as the primary provider for the patient at the study site.

Exclusion Criteria:

For Part A, subjects must not meet any of the following exclusion criteria.
Patients with distant metastatic disease.
Patients with known Ewing-like sarcoma (e.g., BCOR-CCNB3 or CIC-DUX4 translocated small round cell sarcomas) are not eligible.
Patients who are enrolled with an initial diagnosis of Ewing sarcoma and subsequently found to have Ewing-like sarcoma will be replaced. Samples obtained prior to removal from study will be analyzed and reported descriptively. Patients with Ewing-like tumors may continue to provide samples and clinical data until they meet off-study criteria per protocol.
Patients weighing < 5 kg at time of diagnosis
Patients with a second malignant neoplasm
Patients without detectable tumor at the time of study enrollment (ie, complete tumor resection prior to study enrollment)
Patients already receiving tumor-directed therapy at the time of study enrollment except when a pre-treatment baseline sample has already been obtained under a local banking study in DFCI Pediatrics that would be eligible for analysis under this study.
Patients with osteosarcoma with a pelvic primary tumor site Pregnancy
For Part B, subjects must not meet any of the following exclusion criteria.
Patients with known Ewing-like sarcoma (e.g., BCOR-CCNB3 or CIC-DUX4 translocated small round cell sarcomas) are not eligible.
Samples obtained prior to removal from study will be analyzed and reported descriptively. Patients with Ewing-like tumors may continue to provide samples and clinical data until they meet off-study criteria per protocol
Patients weighing < 5 kg at time of enrollment
Patients diagnosed with relapsed disease and/or having started therapy directed at disease relapse
Pregnancy
Resides outside of the United States
For Part B, providers at non-study centers will not be eligible to receive the provider survey.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027-0700
2	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
3	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
4	Boston Children's Hospital	Boston	Massachusetts	United States	02115
5	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
7	Children's Hospital's and Clinics of Minnesota	Minneapolis	Minnesota	United States	55404
8	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
9	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
10	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	Lifespan / Rhode Island Hospital	Providence	Rhode Island	United States	02903
12	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
13	UT Southwestern Medical Center	Dallas	Texas	United States	75390
14	University of Utah Childrens Medical Center	Salt Lake City	Utah	United States	84113
15	Seattle Children's Hospital	Seattle	Washington	United States	98105