Trial Summary
What is the purpose of this trial?This trial is testing a blood test that looks for small pieces of tumor DNA in patients with Ewing sarcoma or osteosarcoma. The goal is to see if this test can help predict if the cancer will return after treatment. A group of patients will participate to help researchers understand how useful this test can be.
Is liquid biopsy a promising treatment for bone cancer?Yes, liquid biopsy is a promising treatment for bone cancer. It offers a non-invasive way to detect and monitor cancer by analyzing blood or other body fluids. This method can help doctors diagnose cancer earlier, track how well treatments are working, and make better decisions about therapy. It's especially useful for bone cancer because traditional biopsies can be painful and risky.357811
What safety data exists for Liquid Biopsy for Bone Cancer?The provided research does not contain safety data for Liquid Biopsy for Bone Cancer or related tests like FoundationOne Liquid CDx. The studies focus on the safety profiles of colony-stimulating factors (CSFs) and filgrastim in cancer treatment, which are unrelated to liquid biopsy tests.124612
What data supports the idea that Liquid Biopsy for Bone Cancer is an effective treatment?The available research shows that Liquid Biopsy, specifically using FoundationOne Liquid CDx, is effective in identifying targetable mutations in bone cancer. In a study involving children and teenagers with high-risk cancers, including bone sarcoma, the liquid biopsy successfully identified molecular changes in 25 out of 45 patients. This allowed for personalized treatment options, with some patients receiving treatments based on these results. Although the study focused on various cancers, it highlights the potential of liquid biopsy to guide treatment decisions in bone cancer by providing important genetic information without the need for invasive procedures.3591011
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should not have started tumor-directed therapy unless a pre-treatment baseline sample was collected. It's best to discuss your current medications with the trial team.
Eligibility Criteria
The LEOPARD trial is for individuals aged 12 months to 50 years with a new diagnosis of Ewing sarcoma or high-grade osteosarcoma, who have not started or just begun treatment. It's not for those with distant metastatic disease, other types of sarcomas, complete tumor resection before joining the study, pelvic primary tumors in osteosarcoma patients, or if pregnant.Inclusion Criteria
I am between 1 year and 50 years old.
I have been diagnosed with Ewing sarcoma, PNET, or high-grade osteosarcoma that is not in my pelvis.
I have only had a biopsy, no surgery to remove my tumor.
I am scheduled to receive chemotherapy.
I have been diagnosed with Ewing sarcoma or PNET of bone or soft tissue.
I am receiving specific chemotherapy protocols for Ewing sarcoma or osteosarcoma.
I am at least 1 year old.
I have only received the first round of treatment for my condition, and maintenance therapy if it was given.
Exclusion Criteria
I have been diagnosed with a second type of cancer.
My tumor was completely removed before joining the study.
My cancer is not Ewing-like sarcoma.
I weigh less than 5 kilograms.
My cancer originates in the bones of my pelvis.
My cancer has spread to distant parts of my body.
I weighed less than 5 kg when my condition was diagnosed.
Treatment Details
This trial tests the use of FoundationOne Liquid CDx liquid biopsy to see how well it predicts outcomes and monitors response to therapy in patients with Ewing sarcoma or osteosarcoma. Participants will be monitored over time to assess changes in ctDNA levels.
2Treatment groups
Experimental Treatment
Active Control
Group I: EWING ctDNA RETURN OF RESULTSExperimental Treatment1 Intervention
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
Group II: REG EWING or OSTEO: ctDNA EVALUATIONActive Control1 Intervention
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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Seattle Children's HospitalSeattle, WA
Childrens Hospital Los AngelesLos Angeles, CA
Children's Healthcare of AtlantaAtlanta, GA
Massachusetts General Hospital Cancer CenterBoston, MA
More Trial Locations
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Who is running the clinical trial?
Dana-Farber Cancer InstituteLead Sponsor
Conquer Cancer FoundationCollaborator
Alex's Lemonade Stand FoundationIndustry Sponsor
Harvard UniversityCollaborator
Sam Day FoundationCollaborator
References
Comparison of G-CSF and GM-CSF adverse event profiles in office-based practices: preliminary study results. [2019]We investigated the adverse event profile of colony-stimulating factors (CSFs) used in office-based oncology practices in the United States. The impetus for the study was anecdotal reports from physicians and nurses working in community practice settings describing the differences in adverse drug events (ADEs) that their-patients experienced with the two CSFs currently available in the United States. The study was a retrospective review of office-based oncology practice records. The frequencies of drug-induced fever and other ADEs secondary to granulocyte (G)-CSF were compared with those of granulocyte-macrophage (GM)-CSF. Adverse drug events were those events that were documented by a clinician as being causally linked to CSF therapy and not obviously due to other causes. This preliminary report of the data indicated that there were some significant differences in the ADEs attributable to either G-CSF or GM-CSF. The appropriate use of CSFs in clinical practice also is discussed.
Canadian supportive care recommendations for the management of neutropenia in patients with cancer. [2021]Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined.
Liquid Biopsy in Solid Malignancy. [2023]The clinical utility of tissue biopsies in cancer management will continue to expand, especially with the evolving role of targeted therapies. "Liquid biopsy" refers to testing a patient's biofluid samples such as blood or urine to detect tumor-derived molecules and cells that can be used diagnostically and prognostically in the assessment of cancer. Many proof-of-concept and pilot studies have shown the clinical potential of liquid biopsies as diagnostic and prognostic markers which would provide a surrogate for the conventional "solid biopsy". In this review, we focus on three methods of liquid biopsy-circulating tumor cells, extracellular vesicles, and circulating tumor DNA-to provide a landscape view of their clinical applicability in cancer management and research.
Evaluation of adverse events associated with filgrastim originator and biosimilar using a spontaneous reporting system database. [2021]Biosimilar products of filgrastim have become available for improved sustainability of cancer care; however, the real-world safety profile remains unknown. The purpose of this study was to clarify the adverse events associated with filgrastim originator and its biosimilar using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between 2014-2018 were extracted. We calculated the reporting odds ratio and 95% confidence interval for each adverse event. We obtained 584 reports of adverse events associated with filgrastim originator and 102 reports with its biosimilar. Signals were detected for bone marrow failure and febrile neutropenia with both filgrastim originator and its biosimilar; whereas those for drug resistance and hypoxia only involved filgrastim originator, and those for interstitial lung disease only involved its biosimilar. The safety profiles of filgrastim originator and its biosimilar were partly different. Further studies are needed to confirm these findings.
Clinical Perspective and Translational Oncology of Liquid Biopsy. [2020]The term liquid biopsy (LB) refers to the study of circulating tumor cells, circulating tumors nucleic acids free of cells or contained in exosomes, and information about platelets associated with tumors. LB can be performed in different biofluids and allows the limitations of tissue biopsy to be overcome offering possibilities of tumor identification reflecting in real time tumor heterogeneity. In addition, LB allows screening and early detection of cancer, real-time monitoring of therapy, stratification and therapeutic intervention, a therapeutic target and resistance mechanism, and a risk of metastatic relapse. Currently, LB has been shown to be effective for its application in different types of tumors including lung, colorectal, prostate, melanoma, breast and pancreatic cancer, by the determination and identification of biomarkers that with a high probability have the potential to change the way in which medical oncology could predict the course of the disease. These biomarkers make it possible to capture the heterogeneity of the cancer, monitor its clonal evolution, indicate new treatments or retreatments and evaluate the responses to different evolutionary and/or therapeutic pressures in the cancer disease.
Risk of secondary hematologic malignancies associated with breast cancer chemotherapy and G-CSF support: A nationwide population-based cohort. [2021]Our study aimed to analyze the risk of hematologic malignancies (HM) associated with the use of G-CSF with chemotherapy for BC. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident breast cancer between 2007 and 2015, who received chemotherapy for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin lymphoma or non-Hodgkin lymphoma (HL/NHL) and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Among a total of 122 373 BC survivors, 38.9% received chemotherapy only and 61.1% received chemotherapy + G-CSF. Overall, 781 cases of hematologic malignancies occurred. We observed a nonsignificant increase in the risk of AML (aHR, 1.3; 95% CI, 1.0-1.7), of MDS (aHR, 1.3; 95% CI, 0.9-1.8) and of ALL/LL (aHR, 2.0; 95% CI, 1.0-4.4) among patients treated by chemotherapy + G-CSF compared to chemotherapy only. In analyses by dose, we observed a slight increase in the risk of AML (1-3 doses: aHR, 1.2; 95% CI, 0.8-1.7/4+ doses: aHR, 1.3; 95% CI, 1.0-1.8) and of MDS (1-3 doses: aHR, 1.1; 95% CI, 0.7-1.7/4+ doses: aHR, 1.4; 95% CI, 1.0-1.9), a significant increase in risk of ALL (1-3 doses: aHR, 1.5; 95% CI, 0.5-3.9 / 4+ doses: aHR, 2.3; 95% CI, 1.0-5.1) with increasing cycles of G-CSF. Our population-based study showed that the ALL/LL was the only HM at increased risk with the use of growth factors with a possible dose-effect relationship. Our data regarding the risk of all the other HM are reassuring.
Liquid biopsies in pediatric oncology: opportunities and obstacles. [2023]Liquid biopsies have emerged as a noninvasive alternative to tissue biopsy with potential applications during all stages of pediatric oncology care. The purpose of this review is to provide a survey of pediatric cell-free DNA (cfDNA) studies, illustrate their potential applications in pediatric oncology, and to discuss technological challenges and approaches to overcome these hurdles.
Recommendations for a practical implementation of circulating tumor DNA mutation testing in metastatic non-small-cell lung cancer. [2022]Liquid biopsy (LB) is a rapidly evolving diagnostic tool for precision oncology that has recently found its way into routine practice as an adjunct to tissue biopsy (TB). The concept of LB refers to any tumor-derived material, such as circulating tumor DNA (ctDNA) or circulating tumor cells that are detectable in blood. An LB is not limited to the blood and may include other fluids such as cerebrospinal fluid, pleural effusion, and urine, among others.
Liquid Biopsy in Colorectal Cancer: Quo Vadis? Implementation of Liquid Biopsies in Routine Clinical Patient Care in Two German Comprehensive Cancer Centers. [2022]The use of liquid biopsies (LB) in patients with solid malignancies enables comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) and has the potential to guide therapy stratification and support disease monitoring. To examine clinical uptake of LB in a real-world setting, LB implementation was analyzed at two German cancer centers (LMU Munich and Charité - Universitätsmedizin Berlin) between 2017 and 2021, with focus on colorectal cancer (CRC) patients.
Blood-Derived Liquid Biopsies Using Foundation One® Liquid CDx for Children and Adolescents with High-Risk Malignancies: A Monocentric Experience. [2022]Precision oncology requires tumor molecular profiling to identify actionable targets. Tumor biopsies are considered as the gold standard, but their indications are limited by the burden of procedures in children. Blood-derived liquid biopsy (LB) is a potential alternative that is not yet documented in real-world settings, especially in pediatric oncology. We performed a retrospective analysis of children and teenagers with a relapsing or refractory disease, upon whom LB was performed using the Foundation One® liquid CDx from 1 January 2020 to 31 December 2021 in a single center. Forty-five patients (27 boys) were included, with a median age of 9 years of age (range: 1.5-17 years old). Underlying malignancies were neuroblastoma (12 patients), bone sarcoma (12), soft tissue sarcoma (9), brain tumors (7), and miscellaneous tumors (5). Forty-three patients had metastatic disease. Six patients had more than one biopsy because of a failure in first LB. Median time to obtain results was 13 days. Overall, analysis was successful for 33/45 patients. Eight patients did not present any molecular abnormalities. Molecular alterations were identified in 25 samples with a mean of 2.1 alterations per sample. The most common alterations concerned TP53 (7 pts), EWS-FLI1 (5), ALK (3), MYC (3), and CREBBP (2). TMB was low in all cases. Six patients received treatment based on the results from LB analysis and all were treated off-trial. Three additional patients were included in early phase clinical trials. Mean duration of treatment was 85 days, with one patient with stable disease after eight months. Molecular profiling using Foundation One® Liquid CDx was feasible in pediatric patients with high-risk solid tumors and lead to identification of targetable mutations in a subset of patients.
Liquid biopsies in primary and secondary bone cancers. [2022]Liquid biopsies are a powerful tool to non-invasively analyze tumor phenotype and progression as well as drug resistance. In the bone oncology field, liquid biopsies would be particularly important to develop, since standard biopsies can be very painful, dangerous (e.g., when found in proximity to the spinal cord), and hard to collect. In this review, we explore the recent advances in liquid biopsies in both primary (osteosarcoma and Ewing sarcoma) and secondary bone cancers (breast, prostate, and lung cancer-induced bone metastases), presenting their current role and highlighting their unexpressed potential, as well as the barriers limiting their possible adoption, including costs, scalability, reproducibility, and isolation methods. We discuss the use of circulating tumor cells, cell-free circulating tumor DNA, and extracellular vesicles for the purpose of improving diagnosis, prognosis, evaluation of therapy resistance, and driving therapy decisions in both primary and secondary bone malignancies.
Prophylaxis of Neutropenia with Lipegfilgrastim in Breast Cancer Patients with Dose-Dense Chemotherapy: Results of a Noninterventional Study on Therapeutic Routine in Germany (NADENS). [2023]Noninterventional study (NIS) on application and effectiveness of primary G-CSF prophylaxis with lipegfilgrastim in primary breast cancer patients undergoing dose-dense (dd) or intense-dose-dense (idd) chemotherapy (CTx) regimen in daily clinical practice.