Radiation, Low-Dose Chemotherapy and Toripalimab Before Surgery for Undifferentiated Pleomorphic Sarcoma

Trial details

Who runs it

Tianjin Medical University Cancer Institute and Hospital

Trial code

NCT07817095

Record updated

14 September 2026

Original description

This is a prospective, single-center, single-arm, open-label phase II exploratory study to evaluate the efficacy, safety, and immune remodeling effects of stereotactic body radiotherapy (SBRT) combined with reduced-dose anthracycline chemotherapy and the PD-1 inhibitor toripalimab as neoadjuvant therapy, followed by postoperative stratified maintenance therapy, in patients with localized high-risk undifferentiated pleomorphic sarcoma (UPS). A Simon two-stage design will be used, with 39 patients planned (stage 1: 13 patients; 35 patients in total, including a 10% dropout rate). Treatment consists of SBRT (8-10 Gy in 5 fractions) followed by toripalimab (240 mg intravenously every 3 weeks, 3 cycles in the neoadjuvant phase) combined with liposomal doxorubicin (30-40 mg/m² intravenously every 3 weeks, 2 cycles in the neoadjuvant phase). After response evaluation, radical surgery is performed. Postoperative stratified maintenance therapy is delivered according to pathological response: patients achieving major pathologic response (MPR) or hyalinized pathologic response (HPR) receive toripalimab monotherapy (240 mg every 3 weeks, up to 14 cycles), while those not achieving MPR/HPR receive toripalimab combined with liposomal doxorubicin (2-4 cycles). The primary endpoint is the rate of major pathologic response (MPR). Secondary endpoints include the rate of hyalinized pathologic response (HPR), radiologic objective response rate (ORR), R0 resection rate, limb salvage rate, and safety.Read full original descriptionShow less

A Single-Arm Phase II Exploratory Study of Neoadjuvant Immunotherapy Plus Chemotherapy Plus SBRT Triplet Therapy and Postoperative Stratified Maintenance Therapy for Undifferentiated Pleomorphic Sarcoma

This is a prospective, single-center, single-arm, open-label phase II exploratory study to evaluate the efficacy, safety, and immune remodeling effects of stereotactic body radiotherapy (SBRT) combined with reduced-dose anthracycline chemotherapy and the PD-1 inhibitor toripalimab as neoadjuvant therapy, followed by postoperative stratified maintenance therapy, in patients with localized high-risk undifferentiated pleomorphic sarcoma (UPS). A Simon two-stage design will be used, with 39 patients planned (stage 1: 13 patients; 35 patients in total, including a 10% dropout rate). Treatment consists of SBRT (8-10 Gy in 5 fractions) followed by toripalimab (240 mg intravenously every 3 weeks, 3 cycles in the neoadjuvant phase) combined with liposomal doxorubicin (30-40 mg/m² intravenously every 3 weeks, 2 cycles in the neoadjuvant phase). After response evaluation, radical surgery is performed. Postoperative stratified maintenance therapy is delivered according to pathological response: patients achieving major pathologic response (MPR) or hyalinized pathologic response (HPR) receive toripalimab monotherapy (240 mg every 3 weeks, up to 14 cycles), while those not achieving MPR/HPR receive toripalimab combined with liposomal doxorubicin (2-4 cycles). The primary endpoint is the rate of major pathologic response (MPR). Secondary endpoints include the rate of hyalinized pathologic response (HPR), radiologic objective response rate (ORR), R0 resection rate, limb salvage rate, and safety.

Inclusion: Male or female, aged 18 to 75 years; Histologically confirmed UPS, screened locally and confirmed by central pathology before enrollment. Adequate IHC (at least CK, S100, SOX10, SMA, desmin, MDM2, CDK4) and NGS when feasible (MDM2/CDK4 amplification mandatory) to exclude dedifferentiated liposarcoma and other differentiated tumors; UPS of extremities or trunk. Max diameter >5 cm, or <=5 cm with any of: encasement of major neurovascular bundle >180 degrees; expected limb functional loss >50% after resection; MDT deems R0 difficult. SBRT-feasible anatomy with >3 mm margin to critical neurovascular structures or joint; Regional nodes evaluated by imaging (US/CT/MRI/PET-CT). Suspicious nodes (short axis >=10 mm, abnormal morphology, or high FDG) require pathology. Uninvolved nodes must not be irradiated; involved nodes included with radical dose or resected; Treatment-naive: no prior chemotherapy, targeted therapy, immunotherapy, or local radiotherapy; At least one measurable lesion per RECIST v1.1; ECOG 0-1; Adequate organ function; Signed ICF, good compliance, willing to provide fresh tumor and blood for translational research.

Exclusion: Other malignancy, except completed treatment with no recurrence/metastasis within 2 years; Major surgery within 4 weeks, or systemic steroids (>10 mg/day prednisone equivalent) or immunosuppressants within 2 weeks; Active infection requiring systemic therapy; active HBV (DNA >=2000 IU/mL), HCV, syphilis, or HIV positive; Active or relapsing autoimmune disease; Severe comorbidity: NYHA >=III, ischemic heart disease, uncontrolled hypertension/diabetes; interstitial lung disease or severe pulmonary impairment; Known active brain metastases; Pregnancy/breastfeeding, or refusal of effective contraception; Any investigator-judged risk to safety or completion.

ClinicalTrials.gov NCT07817095