Clinical Investigation of Sonodynamic Therapy in Conjunction With Chemoradiotherapy for Glioblastoma Management
Trial Snapshot
- Phase
- Phase 2
- Status
- Enrolling By Invitation
- Sponsor
- Enrollment
- 230
- Locations
- 1
- Primary Endpoint
- Progression - free survival (PFS)
Study Overview
Brief 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 This trial builds on Phase I results (unpublished) showing SDT induced tumor shrinkage in recurrent GBM with minimal toxicity.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:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 75 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed informed consent form;
- •Age < 75 years;
- •Newly diagnosed postoperative glioblastoma patients pathologically confirmed as glioblastoma;
- •Absence of severe hematopoietic dysfunction or cardiac, pulmonary, hepatic, renal abnormalities, or immunodeficiency. Pre-enrollment laboratory results must meet the following:
- •Hematology:
- •White blood cell count ≥4×10⁹/L
- •Absolute neutrophil count ≥1.5×10⁹/L
- •Platelets ≥100×10⁹/L
- •Hemoglobin ≥90g/L
- •Renal function:
- •Serum creatinine ≤1.2mg/dL or creatinine clearance ≥60mL/min
- •Hepatic function:
- •Total bilirubin ≤1.5×ULN (≤3.0×ULN if liver metastasis present)
- •AST/ALT ≤2.0×ULN (≤5.0×ULN if liver metastasis present)
- •Coagulation:
- •INR ≤2.0, with PT, APTT, and TT within normal ranges;
- •Life expectancy ≥3 months;
- •Adverse reactions from prior anti-tumor therapy recovered to ≤ Grade 1, or complete recovery from surgery (Investigator's judgment);
- •Fertile females and all male subjects must agree to use highly effective contraception (condoms, sponges, gels, diaphragms, IUDs, oral/injectable contraceptives, or implants) during the trial and for 12 months after last Hematoporphyrin use. Fertile females must have negative pregnancy test within ≤7 days before investigational product administration.
Exclusion Criteria
- •Recurrent glioblastoma, brainstem tumors, or glioblastoma patients having received postoperative chemoradiotherapy;
- •Hypersensitivity to photosensitizers;
- •Uncontrolled infections, refractory epilepsy, and/or intracranial hypertension, and/or hypertension, and/or hyperglycemia;
- •HIV infection, active hepatitis B (HBsAg positive with HBV DNA positive), or hepatitis C (HCV antibody positive);
- •Other malignancies within 5 years without effective control (excluding cervical carcinoma in situ, cutaneous squamous cell carcinoma, or localized basal cell skin cancer);
- •Other Investigator-assessed contraindications for trial participation.
Arms & Interventions
SDT + Standard Therapy
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 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 day1to 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
Intervention: Sonodynamic Therapy (SDT) (Procedure)
SDT + Standard Therapy
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 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 day1to 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
Intervention: Standard Treatment (Other)
Standard Therapy
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
Intervention: Standard Treatment (Other)
Outcomes
Primary Outcomes
Progression - free survival (PFS)
Time Frame: It is evaluated for up to 5 years from the date of randomization to the date of first documented progression or death from any cause, whichever comes first
Secondary Outcomes
- Overall survival time(It is evaluated for up to 5 years from the date of randomization to the date of death from any cause.)
Investigators
Yingjuan Zheng
Chief physician
The First Affiliated Hospital of Zhengzhou University