SBRT Combined With Reduced-Dose Anthracycline Chemotherapy and Toripalimab as Neoadjuvant Therapy for Localized High-Risk Undifferentiated Pleomorphic Sarcoma

NCT07817095 | Not Yet Recruiting Phase 2

• 2 other identifiers: SPARK-UPS-01E20261130
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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

Undifferentiated Pleomorphic Sarcoma (UPS)

Keywords

Undifferentiated pleomorphic sarcoma; Toripalima; SBRT; Liposomal doxorubicin; Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Rate of Major Pathologic Response (MPR)

  At surgery

Secondary Outcomes (5)

• Rate of Hyalinized Pathologic Response (HPR)

  At surgery

• Objective Response Rate (ORR)

  After completion of neoadjuvant therapy, before surgery (approximately weeks 8-9 after enrollment)

• R0 Resection Rate

  At surgery

• Limb Salvage Rate

  At surgery

• Adverse Events

  From the first dose of study treatment until at least 100 days after the last dose

Study Arms (1)

Experimental Arm

EXPERIMENTAL

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%).

Drug: Toripalimab; Drug: Liposomal doxorubicin; Radiation: Stereotactic body radiotherapy (SBRT)

Interventions

Toripalimab DRUG

Toripalimab 240 mg IV q3w; 3 neoadjuvant doses from SBRT start; maintenance up to 14 cycles until progression, death, or unacceptable toxicity.

Experimental Arm

Liposomal doxorubicin DRUG

Liposomal doxorubicin 30-40 mg/m2 IV q3w; 2 neoadjuvant cycles. Non-MPR/HPR: 2-4 adjuvant cycles (2 cycles if HPR \>30%).

Experimental Arm

Stereotactic body radiotherapy (SBRT) RADIATION

SBRT 8-10 Gy x 5 (median 8 Gy x 5), over 5-10 days in weeks 1-3, IGRT required.

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Histiocytoma, Malignant Fibrous

Interventions

toripalimab; liposomal doxorubicin; Radiosurgery

Condition Hierarchy (Ancestors)

Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Jilong Yang

CONTACT

+86-18622221626; yangjilong@tjmuch.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: September 14, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): September 1, 2030
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)