A Study of Ta-NPs Plus Radiotherapy for Locally Recurrent Retroperitoneal Sarcoma

Ta-NPs Combined With Radiotherapy for Locally Recurrent Retroperitoneal Soft Tissue Sarcoma: A Prospective, Single-Arm Clinical Study

This prospective, single-arm, open-label phase I study evaluates the safety and tolerability of intratumoral injection of tantalum nanoparticles (Ta-NPs) followed by radiotherapy in patients with locally recurrent retroperitoneal soft tissue sarcoma. Using a standard 3+3 dose-escalation design, three dose levels of Ta-NPs (injection volumes of 2%, 5%, and 10% of tumor volume, all at 30 mg/mL) are tested in sequential cohorts to identify dose-limiting toxicities.

Inclusion Criteria:

1. Age ≥18 years, male or female.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

3. Histopathologically confirmed diagnosis of dedifferentiated liposarcoma (DD-LPS) or leiomyosarcoma (LMS) with local or regional recurrence after prior standard treatment with curative intent. Prior treatment must include:

   a) Curative/radical or extended resection of the primary or first recurrent lesion. b) Possible prior treatments (if received) must be completed at least 4 weeks before enrollment, including: radiotherapy (external beam radiotherapy to the abdominopelvic region; detailed radiotherapy plan and DVH must be available to assess normal organ doses), chemotherapy (anthracycline- and/or ifosfamide-based systemic chemotherapy), or targeted therapy (e.g., anlotinib). c) All acute adverse events from prior treatments must have resolved to normal or Grade 1 per CTCAE.

4. At least one lesion suitable for intratumoral injection (either directly or under imaging guidance) and radiotherapy, with a volume ≤3000 cm³ (tumor volume = length × width × height measured by CT/MRI), and measurable by imaging.

5. Adequate hematologic and organ function within 7 days before first dose, meeting the following laboratory criteria:

   1. Hematology (without G-CSF within 14 days): Absolute neutrophil count (ANC) ≥1.5×10^9/L; (without platelet transfusion within 14 days): Platelet count (PLT) ≥90×10^9/L; (without red blood cell transfusion or erythropoietin within 14 days): Hemoglobin (Hb) ≥90 g/L.
   2. Renal function: Serum creatinine (Cr) ≤1.5×upper limit of normal (ULN), or calculated creatinine clearance (Cockcroft-Gault) ≥50 mL/min (only required if baseline Cr >1.5×ULN).
   3. Liver function: Total bilirubin (TBIL) ≤1.5×ULN (or ≤3.0×ULN for Gilbert's syndrome or liver metastases); AST, ALT, and alkaline phosphatase (ALP) ≤2.5×ULN; serum albumin ≥2.8 g/dL.
   4. Coagulation: International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5×ULN.
   5. Cardiac: Left ventricular ejection fraction (LVEF) ≥50%.

6. Expected survival ≥6 months.

7. Willing and able to provide written informed consent, good compliance, and able to complete follow-up.

Exclusion Criteria:

1. Presence of distant metastasis (M1 stage) that is not suitable for local radiotherapy intervention.
2. Active skin ulceration, infection, erosion, necrosis, bleeding at the injection site, or risk of hollow organ perforation.
3. The target lesion(s) have received radiotherapy within the past 6 months.
4. Known allergy or intolerance to the active ingredient or excipients of Ta-NPs or similar nanoparticles.
5. Pregnant or breastfeeding women; subjects (or their partners) who plan to become pregnant or have unprotected sexual intercourse without appropriate contraceptive measures (e.g., condoms, intrauterine devices, or partner sterilization) from screening through 3 months after study completion.
6. HIV-positive; HCV-positive; HBsAg-positive or HBcAb-positive with detectable HBV DNA (quantitative assay ≥500 IU/mL).
7. Active pulmonary tuberculosis, or history of pulmonary tuberculosis that has not been controlled after treatment.
8. Other severe, uncontrolled concomitant diseases that may affect protocol compliance or interfere with interpretation of results, including active opportunistic or progressive (severe) infection, uncontrolled diabetes mellitus, cardiovascular disease (New York Heart Association Class III or IV heart failure, second-degree or higher atrioventricular block, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina, cerebral infarction within 3 months, etc.), or pulmonary disease (interstitial pneumonia, obstructive lung disease, symptomatic bronchospasm history).
9. Active central nervous system (CNS) metastases or leptomeningeal disease. Subjects with treated brain metastases may be eligible if there is no evidence of progression on MRI for at least 8 weeks after treatment and within 28 days before first dose, and if systemic corticosteroids (>10 mg prednisone equivalent/day) are not required for at least 2 weeks before study drug administration.
10. Major surgical procedure (excluding diagnostic surgery) within 4 weeks before start of treatment.
11. History of psychoactive substance abuse without ability to abstain, or history of psychiatric disorders.
12. History of other malignancies within the past 5 years, except those that have been clearly cured or are curable, such as basal cell or squamous cell skin cancer, superficial bladder cancer or prostate carcinoma in situ, cervical carcinoma in situ, or breast carcinoma in situ.
13. Any other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that, in the investigator's opinion, may increase the risk associated with study participation or may interfere with the interpretation of study results.
14. Any condition that is not in the best interest of the participant.