TLR4 Agonist GLA-SE and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma That Is Metastatic or Cannot Be Removed by Surgery

PRIMARY OBJECTIVES: I. To evaluate the safety of weekly injections of GLA-SE (TLR4 agonist GLA-SE) in combination with palliative radiation in patients with metastatic sarcoma. SECONDARY OBJECTIVES: I. To look for preliminary evidence of efficacy at distant tumor sites following the combination of radiation and intra-tumor injection of GLA-SE. II. To analyze changes in tumor-immune infiltrates following radiation and intra-tumor injection of GLA-SE. OUTLINE: This is a dose-escalation study of TLR4 agonist GLA-SE. Patients receive TLR4 agonist GLA-SE intratumorally once weekly for 8 weeks. Within 2 weeks of starting treatment, patients also undergo radiation therapy over 2 weeks for a total of 5-6 fractions. After completion of study treatment, patients are followed up every 6 weeks for 6 months and then every 3 months for up to 1 year.