Locally Recurrent Retroperitoneal Soft Tissue Sarcoma
Conditions
Keywords
Retroperitoneal Soft Tissue Sarcoma, Radiotherapy, Radiosensitizer, Nanomaterials
Brief summary
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.
Interventions
BIOLOGICALTa-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.
RADIATIONRadiotherapy
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).
BIOLOGICALTa-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.
BIOLOGICALTa-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.
Sponsors
West China Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicity (DLT) | From day of Ta-NPs injection through day 28 post-injection | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Control Rate at 6 Months | 6 months post injection | Proportion of participants with no disease progression (as defined by RECIST 1.1) at 6 months after intratumoral injection. |
| Progression-Free Survival (PFS) | From injection until disease progression or death (up to approximately 36 months) | Time from intratumoral injection to first documented disease progression (per RECIST 1.1) or death from any cause, whichever occurs first. |
| Overall Survival (OS) | From injection until death (up to approximately 36 months) | Time from intratumoral injection to death from any cause. |
| Salvage Surgery Success Rate | At the time of salvage surgery | Proportion of participants who undergo salvage surgery after treatment and achieve complete (R0) resection. |
| Incidence of Adverse Events | From signing of informed consent through 90 days after last dose | 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. |
| Objective Response Rate (ORR) | 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. | Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria, assessed for injected and non-injected lesions. |
| Pharmacokinetics (PK) of Ta-NPs | 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 | 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). |
Countries
China
Contacts
CONTACTXingchen Peng, MD, PhD
Outcome results
None listed