Neo-adjuvant radiation and intratumoral immunotherapy followed by surgery- NARIS trial for extremity soft tissue sarcoma

Abstract

Extremity soft tissue sarcoma (ESTS) is a rare malignant nonepithelial disease, calling for combined modality treatments with surgery to further improve local control rates and long-term survival, especially in patients with multiple local recurrences with or without risk of amputation. In this double-arm, open-label, Phase II clinical trial, we will enroll 30 patients with pathologically confirmed ESTS without nodal involvement or distant metastases. Patients are randomly assigned to the combination treatment group or the radiation monotherapy group. Additionally, tumor and biological samples will be obtained directly before and after neoadjuvant therapy, allowing for studies of immune response and primary drug resistance mechanisms.Clinical Trial Registration: ChiCTR2200060659 (http://www.chictr.org.cn) (ClinicalTrials.gov).

Keywords: clinical trial; in situ vaccine; intratumoral immunotherapy; neoadjuvant; radiotherapy; soft tissue sarcoma.

Figure 1.

Schema of the study design. Eligible patients are randomly assigned to two arms and receive 2 cycles of neoadjuvant treatment (every 3 weeks) respectively in a 1:1 allocation ratio. “nRS” group receive neoadjuvant hypofractionated radiotherapy alone; “nRIS” group receive neoadjuvant combination treatment with hypofractionated radiotherapy and intratumoral injection of PD-L1 monoclonal antibodies (by dotted lines). HFRT: Hypofractionated radiotherapy; i.t.: Intratumoral; IHC: Immunohistochemistry; IO: Immuno-Oncology; nRT: Neoadjuvant radiotherapy; -seq: Sequencing.