Metastatic Leiomyosarcoma Biomarker Protocol

Study Overview
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Brief Summary
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Leiomyosarcoma (LMS) is one of the most prevalent soft tissue sarcomas (STS) and can occur in various sites including soft tissue, uterus and retroperitoneal large vessels. Metastatic disease occurs in approximately 50% of patients diagnosed with leiomyosarcoma and prognosis is poor in setting of metastatic disease. A minority of patients benefit from treatment with chemotherapy and early biomarkers of benefit from treatment are lacking. 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. Circulating tumor DNA (ctDNA) is present in blood of patients with advanced/metastatic cancer and may serve as biomarker of tumor response to chemotherapy. Blood samples will be collected prior to and during and 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. Study participants will be asked to complete a questionnaire on attitudes and understanding of genetics and genetic testing.

Official Title
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Observational Study of Biomarkers of Disease-related Outcomes in Patients With Metastatic Leiomyosarcoma Receiving Chemotherapy

Conditions
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Leiomyosarcoma

Intervention / Treatment
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* Other: Plasma Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unresectable or metastatic leiomyosarcoma (LMS). There is no age requirement Receiving first-line chemotherapy with doxorubicin or gemcitabine/docetaxel Sum of target lesions per RECIST1.1 of 5 cm or greater Archival tumor tissue including 1 H&E stained slide and unstained tumor tissue (either tissue block containing tumor, or minimum of 4 unstained slides - fresh frozen sample may also be used in lieu of FFPE sample) 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Enrolled Subjects<br>Once enrolled subjects will provide Archival Tissue, Optional Fresh tumor from a biopsy and blood collections at baseline, day 8 of cycle 1, day 1 of cycles 2-6, and at progression. | Other: Plasma Collection<br>* Patients will provide tissue and blood samples. No medical intervention will be completed for study purposes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ctDNA with RECIST | To examine the correlation of change in ctDNA with objective tumor response per RECIST. Analysis will occur at each subsequent early time-point (pre-cycle 1, mid-cycle 1 and pre-cycle 2). | 4 years from study start | 
| Change in ctDNA with progression free survival (PFS) | To examine the correlation of change in ctDNA with progression free survival (PFS). Analysis of ctDNA will occur at each subsequent early time-point (pre-cycle 1, mid-cycle 1 and pre-cycle 2). A Cox regression model will determine whether the baseline ctDNA levels are associated with PFS. | 54 months from study start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of ctDNA in patients with unresectable or metastatic leiomyosarcoma. | Plasma collections for ctDNA analysis will be collected at each subsequent early time-point (pre-cycle 1, mid-cycle 1 and pre-cycle 2). | 4 years from study start | 

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