Clinical trial NCT04925089: Localized Leiomyosarcoma Biomarker Protocol
Official title: Pilot Study of ctDNA and Imaging Characteristics as Biomarkers of Disease-related Outcomes in Patients With Localized Leiomyosarcoma Receiving Chemotherapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Leiomyosarcoma
Keywords: ctDNA
radiomics
biomarker
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2021-06-14
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have been diagnosed with grade 2 or 3, high-grade leiomyosarcoma who have agreed to receive neoadjuvant doxorubicin and ifosfamide combination chemotherapy where the primary tumor is amenable to complete resection

Brief summary: * 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 2 years
measure: To evaluate change in ctDNA in patients with localized, high-grade leiomyosarcoma undergoing preoperative doxorubicin/ifosfamide chemotherapy with or without pre-operative radiation
timeFrame: 2 years
Secondary outcomes:
measure: To examine the association of change in ctDNA and imaging characteristics with 2-year relapse-free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: University of Michigan Rogal Cancer Center
name: Scott Schuetze
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kasper B, Wilky BA. Sounding the Alarm on Leiomyosarcoma Recurrence: Role of Circulating Tumor DNA. Clin Cancer Res. 2022 Jun 13;28(12):2480-2481. doi: 10.1158/1078-0432.CCR-22-0738.