NCT07049848

SATURN-STS: Phase II Study of Neoadjuvant Atezolizumab With Doxorubicin, Concurrent Atezolizumab With Pre-operative Radiation Therapy and Adjuvant Atezolizumab in Patients With High-risk Surgically Resectable Extremity and Truncal Soft Tissue Sarcoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical research study is to look at the effectiveness of giving a combination of chemotherapy, immunotherapy, radiation therapy, and surgery to treat soft tissue sarcomas that can be removed by surgery. Researchers want to find out if this treatment combination can extend the time it takes for the disease to relapse (come back after treatment). The safety of this treatment combination will also be studied.

Detailed description

Primary Objective: The primary objective is to determine time-to relapse (TTR) for patients with high-risk localized, resectable soft tissue sarcomas treated with neoadjuvant doxorubicin chemotherapy with concurrent atezolizumab, followed by preoperative radiotherapy plus atezolizumab, followed by surgery and additional adjuvant atezolizumab. Secondary Objectives: To estimate TTR in each histologic type of disease included. To assess the pathologic response on pre-treatment (diagnostic biopsy), mid-treatment (afterneoadjuvant chemotherapy + immunotherapy), and surgical specimen (after pre-operative RT) in the overall cohort and each histologic type separately by percent viable tumor cells, percent tumor necrosis, and the presence of fibrosis and hyalinization. To assess the objective response rate (ORR) of neoadjuvant atezolizumab and doxorubicin combination therapy and preoperative radiation therapy with atezolizumab by imaging (RECIST 1.1) before surgical resection in the overall cohort and each histologic type separately. To assess the 12-, 24-month, and 60-month local recurrence-free survival (LRFS), distantmetastasis-free survival (DFMS), event-free survival (EFS) and overall survival (OS) of patients in the overall cohort and each histologic type separately. To evaluate the safety of atezolizumab combination therapy with doxorubicin in the neoadjuvant setting, with radiation in the preoperative setting, and as a monotherapy in the adjuvant setting by CTCAE version 5.0 criteria. To assess acute and late radiation toxicities as per the CTCAE, including the development of major wound complications (MWCs) following surgery. Peripheral limb edema will be documented according to the Late Limb Edema Scoring Criteria. Provider-scored extremity function and patient-scored functional assessment will be documented according to the Musculoskeletal Tumour Society Rating Scale (MSTS) and the Toronto Extremity Salvage Score (TESS), respectively. Exploratory Objective: We will aim to profile the tumor immune microenvironment by assessing the immune infiltrate at baseline and in response to neoadjuvant atezolizumab and doxorubicin combination therapy and preoperative radiation therapy with atezolizumab. Investigators will profile the tumor immune microenvironment by immunohistochemistry (IHC) and by performing multiplex immunofluorescence analyses (mIF) including quantitative assessment of tertiary lymphoid structures (TLS), CD20 B-cells, CD8 T cells and PD-L1 expression levels. Investigators will also use immune deconvolution of bulk RNA sequencing (RNAseq) to evaluate the Sarcoma Immune Classes (SIC) and other validated immune signatures. Investigators will also profile intratumoral CD4T, CD8T cell receptor diversity by TCR deep sequencing. Investigators will collaborate with our APOLLO and MOSAIQ rare tumors program here at MD Anderson to achieve the bulk of these exploratory aims as our patients will co-consent to protocol 2014-0938 (Longitudinal Biospecimen Acquisition for All Tumor Types And At-Risk Tissue) for tissue and blood collection. The workflow will be as per below.

Conditions

• Soft Tissue Sarcoma

Interventions

Type	Name	Description
DRUG	Atezolizumab	Given by IV
DRUG	Doxorubicin Hydrochloride	Given by IV

Timeline

• Start date: 2025-09-11
• Primary completion: 2028-01-01
• Completion: 2030-01-01
• First posted: 2025-07-03
• Last updated: 2025-11-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study