NCT07130149

Sonodynamic-Chemoradiotherapy Integration in Glioblastoma

Clinical Investigation of Sonodynamic Therapy in Conjunction With Chemoradiotherapy for Glioblastoma Management

• Status: Enrolling By Invitation
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 230 (estimated)
• Sponsor: Yingjuan Zheng · Academic / Other
• Sex: All
• Age: 75 Years
• Healthy volunteers: Not accepted

Summary

This Phase II trial tests if sonodynamic therapy (SDT)-a non-invasive treatment using ultrasound to activate a cancer-killing drug-improves outcomes for newly diagnosed glioblastoma patients. Who? 230 adults (\<75 years) with confirmed glioblastoma, adequate organ function, no major health issues. Groups: Test Group: SDT + standard therapy (radiation, chemo, bevacizumab). Control Group: Standard therapy alone. Procedure: SDT uses the drug Hiporfin® followed by focused ultrasound sessions. Patients avoid sunlight for 1 month. Study Duration: Treatment: \~6-8 weeks. Follow-up: 24 months (monthly MRIs). Key Goal: Compare progression-free survival (time until tumor worsens) between groups. Secondary goals: overall survival, safety.

Detailed description

Detailed Description This single-center, randomized, open-label Phase II trial evaluates the synergistic efficacy and safety of sonodynamic therapy (SDT) combined with standard chemoradiotherapy in newly diagnosed glioblastoma (GBM). While the Brief Summary outlines the trial's scope, this section elaborates on mechanistic, methodological, and analytical nuances not captured elsewhere. Scientific Rationale SDT leverages low-intensity, low-frequency focused ultrasound (LILFU) (800 kHz-1 MHz, 1-1.25 W/cm²) to activate the sonosensitizer Hiporfin® (5 mg/kg), generating cytotoxic reactive oxygen species (ROS) selectively within tumor cells. Preclinical data demonstrate SDT disrupts mitochondrial function, enhances DNA damage from temozolomide, and promotes immunogenic cell death. This trial builds on Phase I results (unpublished) showing SDT induced tumor shrinkage in recurrent GBM with minimal toxicity. Intervention Specifics SDT Protocol: Timing: Initiated 40 hours post-Hiporfin® administration to optimize tumor drug accumulation. Ultrasound Parameters: Frequency: 800 kHz-1 MHz (adjustable for tumor depth). Intensity: 1-1.25 W/cm² (below cavitation threshold to minimize tissue damage). Duration: 15 minutes/session, repeated at 24h, 48h, and 72h. Localized Delivery: Adults receive Hiporfin® via intra-arterial infusion (maximizing tumor uptake); children receive intravenous dosing (safety precaution). Standard Therapy: Radiation: 50-54 Gy in 1.8-2 Gy fractions (25 sessions). Temozolomide: 75 mg/m²/day concurrent with radiation; escalated to 150-200 mg/m²/day post-radiation. Bevacizumab: 7.5-10 mg/kg every 3 weeks (angiogenesis inhibition). Methodological Rigor Stratified Randomization: Patients are stratified by tumor location (supratentorial vs. deep midline), size (\<4 cm vs. ≥4 cm), and residual post-surgical volume to balance prognostic factors. Imaging Protocol: MRI scans (T1-weighted with contrast, FLAIR) are standardized across timepoints (baseline, monthly post-treatment) and analyzed centrally using 3D volumetric segmentation to reduce inter-rater variability. Safety Monitoring: Phototoxicity Mitigation: Strict 30-day light avoidance protocol with ambient light levels monitored. Real-Time AE Tracking: Adverse events (e.g., skin reactions, CNS edema) are graded per WHO criteria and managed via a pre-specified escalation algorithm. Statistical Analysis Primary Endpoint: Progression-free survival (PFS) analyzed via stratified log-rank test (α=0.05, two-sided), adjusting for stratification factors. Secondary Endpoints: Overall survival (OS) analyzed using Weibull parametric survival models. Tumor control rate (CR+PR+SD) assessed via RECIST 1.1 with RANO criteria for neurologic tumors. Exploratory Analysis: Biomarker correlation (EGFR expression, ROS levels) with SDT response using multiplex IHC and RNA sequencing. Innovation \& Impact This trial is the first to integrate SDT with standard GBM therapy in a randomized design. If successful, SDT could address critical unmet needs: Non-invasive targeting of deep/inoperable tumors. ROS-mediated chemo/radio-sensitization to overcome treatment resistance. Reduced neurotoxicity vs. traditional therapies.

Conditions

• Glioblastoma (GBM)

Interventions

Type	Name	Description
PROCEDURE	Sonodynamic Therapy (SDT)	SDT: Hematoporphyrin 5 mg/kg.Sonodynamic therapy is administered 40 hours later, twice a day with an interval of 10-12 hours, for 5 consecutive days. One cycle lasts 28 days, and a total of 4-6 cycles are conducted.
OTHER	Standard Treatment	Radiotherapy: The dose is 50-54 Gy, 1.8-2 Gy per day, 5 times a week, for a total of 25 sessions Chemotherapy: When temozolomide is administered concurrently with radiotherapy, the dose is 75 mg/m² per day, taken daily until the end of radiotherapy. For adjuvant chemotherapy with temozolomide, the dose is 150 mg/m² per day from day 1 to day 5, followed by a 23 - day rest period. Each cycle lasts 28 days. If well - tolerated, the dose should be adjusted to 200 mg/m² per day for the 2nd - 6th cycles Targeted Therapy: Bevacizumab 7.5-10 mg/kg, once every 3 weeks, for a total of 4-6 courses

Timeline

• Start date: 2024-10-01
• Primary completion: 2028-08-01
• Completion: 2028-10-01
• First posted: 2025-08-19
• Last updated: 2025-08-19

Locations

1 site across 1 country: China