IRB Study Number 20-970
Status Recruiting
Institutes Taussig Cancer Institute, Pediatric Institute
Description
Primary Objective
To test whether continuing detection of cell-free plasma tumor DNA (ptDNA) when a patient is in radiographic remission 2-3 weeks after local control can predict recurrence in pediatric sarcomas which include fusion positive sarcomas and osteosarcomas.
To test whether the continuing presence of circulating tumor cells (CTC), when a patient is otherwise in radiographic remission 2-3 weeks after local control, can predict recurrence of pediatric sarcomas.
Secondary Objectives
To test whether the decrease of ptDNA burden following the initial cycle of therapy, can predict the five-year recurrence free survival of patients with pediatric sarcomas.
To test whether the CTC or ptDNA burden detected in newly diagnosed patients before local control or chemotherapy can predict the five-year recurrence free survival of patients with pediatric sarcomas.
Exploratory Objectives
To characterize the plasma cytokine levels in patients with high-risk pediatric sarcoma patients.
To demonstrate the feasibility of discovering the clonal evolution in pediatric sarcoma patients through plasma tumor DNA and tumor analysis.
To explore the feasibility of performing single cell RNA-seq on CTC samples collected through a multi-center consortium.
To explore the feasibility of detecting fusion genes such as, but not limited to SYT-SSX1/SSX2, EWS-WT1, CIC-DUX4, and BCOR-CCNB3 from the ptDNA of patients with fusion gene positive sarcomas.
To explore the detailed kinetics of ptDNA release during early stage chemotherapy administration.
Inclusion Criteria
1 Patients must be ≤ 40 years of age
2 Patients must be newly diagnosed. They must not have received any systemic agents for therapy for this new diagnosis
3 Patients with a suspected or confirmed diagnosis of one of the following solid tumors listed below. Histologic or cytological confirmation of the diagnosis is not required at enrollment, but must be resulted within 1 month of enrollment, which will be used to stratify patients into the five separate cohorts listed below. The assigned cohorts are used only for statistical analysis.
• Cohort 1, Ewing sarcoma: confirmed or suspected diagnosis of Ewing sarcoma with a t(11;22) EWS-FLI1 or t(21;22) EWS-ERG translocation.
• Cohort 2, Fusion gene positive rhabdomyosarcoma: confirmed or suspected diagnosis of a rhabdomyosarcoma with a t(2;13) PAX3-FOXO1 or t(1;13) PAX7-FOXO1 translocation.
Please Note: For cohort 1 (Ewing sarcoma) and 2 (fusion gene positive rhabdomyosarcoma), the results of the molecular diagnosis are not required to be resulted upon study enrollment, but required to be sent and pending. While we anticipate there are many occasions where the molecular diagnosis is discovered to be not EWS-FLI1, EWS-ERG, or FOXO1 rearranged. In these situations, the patients can still be enrolled in cohort 5.
• Cohort 3, Fusion gene negative rhabdomyosarcoma: Newly diagnosed patients with a confirmed or suspected diagnosis of a rhabdomyosarcoma without a t(2;13) PAX3-FOXO1 or t(1;13) PAX7-FOXO1 translocation.
• Cohort 4, Osteosarcoma: Newly diagnosed patients with a confirmed or suspected diagnosis of an osteosarcoma.
• Cohort 5, fusion gene positive sarcomas not in cohort 1 and 2, (synovial sarcoma, Ewing like sarcomas, any other EWRS, FUS or other translocation considered to be a sarcoma such as, but not limited toCIC-DUX4, and BCOR-CCNB3, and other fusions in sarcomas that can be detected by the assays).
4 Availability of archival tumor tissue. While snap-frozen tissue is strongly recommended, in select cases, non-decalcified FFPE tissue blocks can be used as an alternative if there is enough appropriately preserved tissue available to analyze for baseline fusion gene status and sequencing. Tumor tissue will be used to analyze patient specific mutations to be used as targets in later analysis of ptDNA through panel sequencing. Patients who do not have appropriate archival tissue, and do not have a planned resection in the future (for example, patients who will utilize radiation only as a local control measure) will be not eligible. For patients who were not able to submit a tumor sample from the initial diagnostic biopsy, but have a surgical resection planned after neoadjuvant chemotherapy, tumor samples can be submitted at this resection as an alternative and patients will be eligible.
5 Patients must have the ability to understand and the willingness to sign a written informed consent or assent document.
Exclusion Criteria
1 Patients that weigh < 8kg.
2 Patients who in the opinion of the investigator may not be able to comply with the requirements of the study are not eligible.
