Evaluating blood tests for Ewing sarcoma and osteosarcoma prognosis

Liquid Biopsy in Ewing Sarcoma and Osteosarcoma As a Prognostic and Response Diagnostic: the LEOPARD Study

This study is testing if blood tests that look for cancer DNA can help predict how well treatment will work for people with Ewing sarcoma or osteosarcoma.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 340 (estimated)
• Ages: 12 Months to 50 Years
• Sex: All
• Sponsor: Dana-Farber Cancer Institute (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 15 sites (Los Angeles, California and 14 other locations)
• Trial ID: NCT06068075 on ClinicalTrials.gov

What this trial studies

This study aims to assess the prognostic value of circulating tumor DNA (ctDNA) in patients diagnosed with Ewing sarcoma or osteosarcoma. Participants will provide blood samples at specific times to detect genetic alterations associated with these cancers. The study is divided into two parts: Part A focuses on identifying ctDNA without returning results to participants, while Part B compares commercial ctDNA testing with research testing. Approximately 150 patients will be enrolled across multiple centers.

Who should consider this trial

Good fit: Ideal candidates are patients aged 12 months to 50 years with newly diagnosed Ewing sarcoma or osteosarcoma who have not yet started chemotherapy or radiation therapy.

Not a fit: Patients who have previously undergone tumor resection or those with pelvic osteosarcoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve the ability to predict cancer recurrence in patients with Ewing sarcoma and osteosarcoma.

How similar studies have performed: Other studies have shown promise in using ctDNA for cancer prognosis, indicating that this approach may be beneficial.

Eligibility criteria

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.

Where this trial is running

Los Angeles, California and 14 other locations

• Childrens Hospital Los Angeles — Los Angeles, California, United States (Recruiting)
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States (Recruiting)
• Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States (Recruiting)
• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• Children's Hospital's and Clinics of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (Recruiting)
• Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
• Lifespan / Rhode Island Hospital — Providence, Rhode Island, United States (Recruiting)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
• UT Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• University of Utah Childrens Medical Center — Salt Lake City, Utah, United States (Recruiting)
• Seattle Children's Hospital — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: David S Shulman, MD — Dana-Farber Cancer Institute
• Study coordinator: David S. Shulman, MD

Conditions 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; High-grade osteosarcoma