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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9
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.
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.
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.
Sichuan University West China Hospital, Chengdu, Sichuan
Chengdu, Sichuan, China
Incidence of Dose-Limiting Toxicity (DLT)
DLT is defined as any adverse event occurring during the DLT observation period (from the first intratumoral injection of Ta-NPs through Day 28 post-injection) that is judged by the investigator to be at least possibly related to Ta-NPs and meets prespecified DLT criteria.
Time frame: From day of Ta-NPs injection through day 28 post-injection
Incidence of Adverse Events
Incidence, severity, and causality of adverse events (AEs), treatment-emergent AEs (TEAEs), Grade ≥3 treatment-related AEs (TRAEs), serious AEs (SAEs), and injection site toxicity (including extravasation) assessed by CTCAE v6.0.
Time frame: From signing of informed consent through 90 days after last dose
Pharmacokinetics (PK) of Ta-NPs
Concentration-time profiles and derived PK parameters of tantalum element in whole blood, plasma, and urine after intratumoral injection of Ta-NPs, measured by inductively coupled plasma mass spectrometry (ICP-MS).
Time frame: 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)
Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria, assessed for injected and non-injected lesions.
Time frame: 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
Proportion of participants with no disease progression (as defined by RECIST 1.1) at 6 months after intratumoral injection.
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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).
Time frame: 6 months post injection
Progression-Free Survival (PFS)
Time from intratumoral injection to first documented disease progression (per RECIST 1.1) or death from any cause, whichever occurs first.
Time frame: From injection until disease progression or death (up to approximately 36 months)
Overall Survival (OS)
Time from intratumoral injection to death from any cause.
Time frame: From injection until death (up to approximately 36 months)
Salvage Surgery Success Rate
Proportion of participants who undergo salvage surgery after treatment and achieve complete (R0) resection.
Time frame: At the time of salvage surgery