Liquid Biopsy as a Prognostic and Response Diagnostic in Patients with Ewing Sarcoma and Osteosarcoma, LEOPARD Study
12 Months and older, Male and Female
18-138 (primary)
NCI-2023-07461
Summary
This study evaluates whether circulating tumor deoxyribonucleic acid (ctDNA) in the blood can provide information about the chances of Ewing sarcoma or osteosarcoma coming back after treatment and locate specific genetic alterations. Identification of patients with Ewing sarcoma or osteosarcoma that has not spread to other parts of the body (localized) at high-risk of disease coming back after a period of improvement (relapse) after standard therapy remains challenging. While a range of prognostic (prediction of the course and outcome of disease processes) factors have been evaluated in these diseases, the presence of metastatic disease (has spread from where it first started [primary site] to other places in the body) remains the strongest adverse prognostic factor at diagnosis. DNA is the substance used to store genetic instructions used for growth, development and functioning of all living things. DNA instructs normal cells and cancer cells. New tests to analyze DNA can detect DNA in the blood that came from tumor cells, called ctDNA. While ctDNA can provide valuable information for patients with some types of adult cancers, it is not yet known whether ctDNA is important in cancers such as Ewing sarcoma or osteosarcoma that impact younger people. By studying patient blood samples, this study may help doctors find better ways to diagnose and treat Ewing sarcoma and osteosarcoma.
Objectives
PRIMARY OBJECTIVE:
I. To determine whether the presence of ctDNA in the peripheral blood is associated with an inferior event-free survival in patients with newly diagnosed, localized Ewing sarcoma or osteosarcoma.
SECONDARY OBJECTIVES:
I. To determine whether a higher level of ctDNA in the peripheral blood is associated with an inferior event-free survival or overall survival in patients with newly diagnosed, localized Ewing sarcoma or osteosarcoma.
II. To estimate the prevalence of detectable ctDNA at diagnosis among patients with localized Ewing sarcoma or osteosarcoma.
III. To evaluate whether the detection of ctDNA at diagnosis is associated with clinical features in patients with Ewing sarcoma or osteosarcoma.
IV. To evaluate whether the change in ctDNA from diagnosis to pre-specified time points is prognostic of event-free survival (EFS) or overall survival in patients with localized Ewing sarcoma or osteosarcoma.
V. To describe the capacity of multiple ctDNA assays to detect key genetic features in Ewing sarcoma (i.e. STAG2 loss and TP53 mutation) and osteosarcoma (i.e. 8q gain) from the peripheral blood.
VI. To compare the EFS in patients with localized Ewing sarcoma or osteosarcoma by detection of genetic features in ctDNA.
VII. To determine whether the presence of ctDNA in the peripheral blood is associated with an inferior overall survival in patients with newly diagnosed, localized, Ewing sarcoma or osteosarcoma.
VIII. To determine the impact of return of ctDNA results at end of therapy and during surveillance on patients, families and clinicians.
EXPLORATORY OBJECTIVES:
I. To perform deep sequencing of ctDNA with the goal of discovering tumor genomic features not previously identified in ctDNA.
II, To explore the incidence of germline features identified through sequencing of cell-free DNA and DNA from white blood cells.
III. To explore the feasibility of detection and profiling of circulating tumor cells in the peripheral blood of patients with Ewing sarcoma or osteosarcoma.
IV. To use leftover blood samples to develop a well annotated biorepository from patients with newly diagnosed Ewing sarcoma or osteosarcoma, along with key clinical data for future research.
V. To characterize ctDNA levels following completion of therapy in patients with localized and metastatic Ewing sarcoma using multiple ctDNA assays (next-generation sequencing [NGS]- and polymerase chain reaction [PCR]-based assays).
OUTLINE: Patients are assigned to 1 of 2 groups.
PART A: Patients undergo blood sample collection throughout the study. Physicians and patients do not receive any return of results of the ctDNA analysis on study.
PART B: Patients undergo blood sample collection during follow-up. Physicians receive ctDNA return of results and discuss results with patients/parents. Patients/parents and providers complete surveys prior to receipt of first ctDNA return of results and after discussion of ctDNA return of results.
After completion of study, patients are followed up for 5 years.
Eligibility
- PART A: >= 12 months of age at time of study enrollment to 50 years of age
- PART A: 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;
- PART A: 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
- PART A: Patients should have only previously had a biopsy, and not had prior attempt at tumor resection
- PART A: 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 Dana-Farber Cancer Institute (DFCI) Pediatrics and is available to use for this study
- PART A: Planned to receive chemotherapy as follows:
* Vincristine, doxorubicin, cyclophosphamide (VDC)/ifosfamide etoposide (IE) as per Children's Oncology Group (COG) protocols AEWS0031, AEWS1031 or AEWS1221 (for patients with Ewing sarcoma or PNET); or
* Methotrexate, doxorubicin, and cisplatin (MAP) as per COG protocol AOST0331 (for patients with osteosarcoma)
- PART B: >= 12 months of age at time of study enrollment
- PART B: Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) of bone or soft tissue
- PART B: Patients should have had only frontline therapy as per institutional standard, and maintenance therapy if given (no relapse therapy)
- PART B: If frontline systemic therapy already completed (not including maintenance or metastatic site radiation), therapy completed within 6 months of enrollment to Part B
- PART B: Subjects must have a willing physician provider supporting their participation in Part B
- 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
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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