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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат Ta-NPs (2% Tumor Volume)
  Ta-NPs at a concentration of 30 mg/mL administered via intratumoral injection at a volume equal to 2% of the baseline tumor volume (calculated as length × width × height). Injection is performed under imaging guidance (ultrasound/CT) prior to radiotherapy.
• Биопрепарат Ta-NPs (5% Tumor Volume)
  Ta-NPs at a concentration of 30 mg/mL administered via intratumoral injection at a volume equal to 5% of the baseline tumor volume (calculated as length × width × height). Injection is performed under imaging guidance (ultrasound/CT) prior to radiotherapy.
• Биопрепарат Ta-NPs (10% Tumor Volume)
  Ta-NPs at a concentration of 30 mg/mL administered via intratumoral injection at a volume equal to 10% of the baseline tumor volume (calculated as length × width × height). Injection is performed under imaging guidance (ultrasound/CT) prior to radiotherapy.
• Лучевая терапия Radiotherapy
  External beam radiotherapy delivered using a medical linear accelerator (energy ≥6 MV X-ray) with image-guided radiotherapy (IGRT). Techniques include intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). Total dose follows NCCN/CSCO guidelines for soft tissue sarcoma. Fractionation: conventional fractionation (1.8-2.0 Gy per fraction, once daily, 5 days per week).

Первичные конечные точки

• Incidence of Dose-Limiting Toxicity (DLT) [Срок оценки: From day of Ta-NPs injection through day 28 post-injection]

Вторичные конечные точки (7)

• Incidence of Adverse Events [Срок оценки: From signing of informed consent through 90 days after last dose]
• Pharmacokinetics (PK) of Ta-NPs [Срок оценки: Blood: Day 0 (pre-injection, 0 hour), and at 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, Day 4, Day 8, Day 15, Day 28; Urine: Collected in intervals: 0-6 hours, 6-12 hours, 12-24 hours (Day 1), Day 2, Day 8, Day 15]
• Objective Response Rate (ORR) [Срок оценки: Assessed at Week 3 (±2 days) after start of treatment, at treatment completion, and at Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, and Month 24 post-treatment initiation.]
• Local Control Rate at 6 Months [Срок оценки: 6 months post injection]
• Progression-Free Survival (PFS) [Срок оценки: From injection until disease progression or death (up to approximately 36 months)]
• Overall Survival (OS) [Срок оценки: From injection until death (up to approximately 36 months)]
• Salvage Surgery Success Rate [Срок оценки: At the time of salvage surgery]

Критерии участия

Критерии включения

• Age ≥18 years, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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.

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

• 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.
• 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).
• 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.
• Coagulation: International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5×ULN.
• Cardiac: Left ventricular ejection fraction (LVEF) ≥50%.
• Expected survival ≥6 months.
• Willing and able to provide written informed consent, good compliance, and able to complete follow-up.

Критерии исключения

• Presence of distant metastasis (M1 stage) that is not suitable for local radiotherapy intervention.
• Active skin ulceration, infection, erosion, necrosis, bleeding at the injection site, or risk of hollow organ perforation.
• The target lesion(s) have received radiotherapy within the past 6 months.
• Known allergy or intolerance to the active ingredient or excipients of Ta-NPs or similar nanoparticles.
• 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.
• HIV-positive; HCV-positive; HBsAg-positive or HBcAb-positive with detectable HBV DNA (quantitative assay ≥500 IU/mL).
• Active pulmonary tuberculosis, or history of pulmonary tuberculosis that has not been controlled after treatment.
• 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).
• 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.
• Major surgical procedure (excluding diagnostic surgery) within 4 weeks before start of treatment.
• History of psychoactive substance abuse without ability to abstain, or history of psychiatric disorders.
• 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.
• 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.
• Any condition that is not in the best interest of the participant.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sichuan University West China Hospital, Chengdu, Sichuan — Чэнду

Публикации

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• Leite ETT, Munhoz RR, Camargo VP, Lima LGCA, Rebolledo DCS, Maistro CEB, Busnardo FF, Ferreira FO, Salvajoli JV, Carvalho HA. Neoadjuvant stereotactic ablative radiotherapy (SABR) for soft tissue sarcomas of the extremities. Radiother Oncol. 2021 Aug;161:222-229. doi: 10.1016/j.radonc.2021.06.027. Epub 2021 Jun 22. PMID 34171452
• Rhomberg W, Hassenstein EO, Gefeller D. Radiotherapy vs. radiotherapy and razoxane in the treatment of soft tissue sarcomas: final results of a randomized study. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):1077-84. doi: 10.1016/s0360-3016(96)00433-6. PMID 8985029
• Rhomberg W. The radiation response of sarcomas by histologic subtypes: a review with special emphasis given to results achieved with razoxane. Sarcoma. 2006;2006(1):87367. doi: 10.1155/SRCM/2006/87367. PMID 17040092
• Khokhar MA, Akhtar M, Shah Gillani SFUH, Abdulsalaam R, Qamar S. Radiotherapy alone with concurrent chemoradiotherapy plus temozolamide in locally advanced soft tissue sarcoma at Mayo Hospital Lahore: A randomized controlled trial. J Pak Med Assoc. 2020 Apr;70(4):572-576. doi: 10.5455/JPMA.293442. PMID 32296197
• Huang Z, Li N, Tang Y, Jin J, Liu W, Xu H, Yu F, Hao L, Zhang Q, Ding Y, Niu X. Neoadjuvant radiotherapy for soft tissue sarcoma in China: a preliminary result. Ann Transl Med. 2022 Apr;10(8):452. doi: 10.21037/atm-22-98. PMID 35571451
• Hayes AJ, Nixon IF, Strauss DC, Seddon BM, Desai A, Benson C, Judson IR, Dangoor A. UK guidelines for the management of soft tissue sarcomas. Br J Cancer. 2025 Jan;132(1):11-31. doi: 10.1038/s41416-024-02674-y. Epub 2024 May 11. PMID 38734790
• Hogg HD, Manas DM, Lee D, Dildey P, Scott J, Lunec J, French JJ. Surgical outcome and patterns of recurrence for retroperitoneal sarcoma at a single centre. Ann R Coll Surg Engl. 2016 Mar;98(3):192-7. doi: 10.1308/rcsann.2016.0057. Epub 2016 Feb 14. PMID 26876538

Идентификаторы

NCT: NCT07578506 · HX 2026-937

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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