Clinical trial · Interventional
SBRT Combined With Reduced-Dose Anthracycline Chemotherapy and Toripalimab as Neoadjuvant Therapy for Localized High-Risk Undifferentiated Pleomorphic Sarcoma
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 15, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260915-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Undifferentiated Pleomorphic Sarcoma (UPS) | Undifferentiated Pleomorphic Sarcoma | ONTOLOGY_EXACT | 0.85 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Liposomal doxorubicin | Drug | — | UNRESOLVED |
| Stereotactic body radiotherapy (SBRT) | Radiation | — | UNRESOLVED |
| Toripalimab | Drug | Toripalimab | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Experimental Arm
- description
- Single-arm. All enrolled patients receive triplet neoadjuvant therapy: SBRT (8-10 Gy in 5 fractions, alternate days or consecutively) first, with concurrent toripalimab (240 mg IV q3w, 3 neoadjuvant cycles) plus liposomal doxorubicin (30-40 mg/m2 IV q3w, 2 neoadjuvant cycles). Radical surgery at weeks 10-12. Postoperative stratified maintenance within 4-8 weeks: MPR/HPR -\> toripalimab 240 mg q3w up to 14 cycles; non-MPR/HPR -\> toripalimab q3w 14 cycles plus liposomal doxorubicin 2-4 cycles (2 cycles if HPR \>30%).
- interventionNames
- Drug: Toripalimab
- Drug: Liposomal doxorubicin
- Radiation: Stereotactic body radiotherapy (SBRT)
Primary outcomes (1)
- measure
- Rate of Major Pathologic Response (MPR)
- timeFrame
- At surgery
Secondary outcomes (5)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
Inclusion Criteria: Inclusion Criteria: 1. Male or female, aged 18 to 75 years. 2. 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. 3. 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. 4. 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. 5. Treatment-naive: no prior chemotherapy, targeted therapy, immunotherapy, or local radiotherapy. 6. At least one measurable lesion per RECIST v1.1. 7. ECOG 0-1. 8. Adequate organ function. 9. Signed ICF, good compliance, willing to provide fresh tumor and blood for translational research. Exclusion Criteria: 1. Other malignancy, except completed treatment with no recurrence/metastasis within 2 years. 2. Major surgery within 4 weeks, or systemic steroids (\>10 mg/day prednisone equivalent) or immunosuppressants within 2 weeks. 3. Active infection requiring systemic therapy; active HBV (DNA \>=2000 IU/mL), HCV, syphilis, or HIV positive. 4. Active or relapsing autoimmune disease. 5. Severe comorbidity: NYHA \>=III, ischemic heart disease, uncontrolled hypertension/diabetes; interstitial lung disease or severe pulmonary impairment. 6. Known active brain metastases. 7. Pregnancy/breastfeeding, or refusal of effective contraception. 8. Any investigator-judged risk to safety or completion.
References
Publications (0)
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