Localized Leiomyosarcoma Biomarker Protocol

Study Overview
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Brief Summary
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Leiomyosarcoma (LMS) is one of the more common soft tissue sarcomas (STS). Patients presenting with large, high-grade, localized LMS are at significant risk of developing metastasis following curative surgery. Clinical trials of neoadjuvant or adjuvant anthracycline and ifosfamide have suggested that patients with localized STS who are at high-risk of metastasis may benefit from chemotherapy, but the magnitude of benefit in unselected patient population is relatively small. Currently, patient age, and tumor size and grade are used to assess risk of metastases and survival Studies evaluating tumor response by imaging and histopathology have not established correlation between tumor characteristics as biomarkers for risk of metastasis or sarcoma recurrence. Circulating tumor DNA (ctDNA) is present in blood of patients with advanced/metastatic LMS and may serve as biomarker of tumor response to chemotherapy. Blood samples will be collected prior to, during and after chemotherapy and analyzed for ctDNA and for mutations in genes that are associated with increased risk of developing sarcoma. Tumor tissue will be collected and analyzed for changes in genes. Digital images of the sarcoma from CT or MRI scans obtained during treatment will be obtained for advanced radiomic analysis. Patients will be followed for 2 years after study entry for signs of sarcoma recurrence. A biomarker of tumor response and patient survival benefit from chemotherapy early in the course of chemotherapy would be of significant impact in treatment planning.

Official Title
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Pilot Study of ctDNA and Imaging Characteristics as Biomarkers of Disease-related Outcomes in Patients With Localized Leiomyosarcoma Receiving Chemotherapy

Conditions
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Leiomyosarcoma

Intervention / Treatment
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* Other: Blood and Tissue collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with localized leiomyosarcoma (LMS) of extremity, body wall or retroperitoneum Grade 2 or 3, or high-grade LMS Tumor size >5 cm in greatest dimension Primary tumor amenable to complete resection There is no age requirement Participant agrees to receive neoadjuvant doxorubicin and ifosfamide combination chemotherapy If pre-operative radiation is administered, it must be administered after chemotherapy. Post-operative radiation may be administered Archival tumor tissue (either frozen sample, tissue block containing tumor, or minimum of 4 unstained slides and 1 H&E stained slide) from diagnostic or pre-treatment biopsy available for study research
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Blood and Tissue collection|Blood and tissue will be collected and analyzed for detection of ctDNA and genetic change|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the association between tumor characteristics assessed by contrast-enhanced MRI and location with presence of circulating tumor DNA (ctDNA) in patients with localized, high-grade leiomyosarcoma | Tumor characteristics from imaging will be compared to the presence of circulating tumor DNA , obtained from blood samples over multiple time points | 2 years | 
| To evaluate change in ctDNA in patients with localized, high-grade leiomyosarcoma undergoing preoperative doxorubicin/ifosfamide chemotherapy with or without pre-operative radiation | Blood will be collected at multiple timepoints. The presence of ctDNA will be assessed prior to, during, and after treatment with chemotherapy and / or radiation | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine the association of change in ctDNA and imaging characteristics with 2-year relapse-free survival | The change in the presence of ctDNA from serial blood collection will be compared to the absence of sarcoma recurrence or after 2 years | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ctDNA, radiomics, biomarker