A Study of Sonodynamic Therapy Using SONALA-001 and Exablate 4000 Type 2.0 in Subjects With Recurrent GBM
- Conditions
- Recurrent GBM
- Interventions
- Combination Product: SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS)
- Registration Number
- NCT05370508
- Lead Sponsor
- SonALAsense, Inc.
- Brief Summary
The primary objectives of this trial are to evaluate the safety, dose-limiting toxicities, maximum tolerated dose (MTD), maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) for future study after a single treatment of SONALA-001 in combination with MRgFUS and to evaluate preliminary efficacy of sonodynamic therapy (SDT) using SONALA-001 and Exablate Type 2.0 device in subjects with progressive or recurrent GBM.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 2 SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS) 10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 2 Cohort 3 SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS) 10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 3 Cohort 1 SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS) 10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 1 Cohort 4 SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS) 10 mg/kg IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 4 Cohort 5 SONALA-001 (ALA) and MR-Guided Focused Ultrasound device (MRgFUS) Recommended Phase 2 Dose (RP2D) IV SONALA-001 (ALA) and MR-guided Focused Ultrasound (MRgFUS) Energy Level 5
- Primary Outcome Measures
Name Time Method To determine Maximum Administered Dose (MAD), Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) after a single treatment of MR-guided Focused Ultrasound (MRgFUS) energy in combination with SONALA-001 SDT (Phase 1) Up to 3 weeks post treatment Determination of Recommended Phase 2 Dose of SONALA-001 SDT in combination with MRgFUS
Safety and Tolerability of SONALA-001 SDT as assessed by the frequency and severity of dose-limiting toxicities (DLTs) Day 1 to Day 21 post treatment Safety and tolerability of SONALA-001 SDT
Definitions of Dose Limiting Toxicities (DLTs):
The DLT window is the 21-day period following the first study treatment per patient.
DLTs are defined as the following events during the DLT window, not clearly related to underlying disease, disease progression or intercurrent illness, as determined by safety review committee:
Any death
Non-hematologic toxicity:
Any CTCAE Grade 3 or higher Hy's law cases Moderate heating/burning at the scalp Grade 3 or greater neurological toxicities Evidence of clinically significant tissue damage outside the region targeted by MRgFUS Grade 3 or greater photosensitivity in subjects strictly following restrictions to light exposure to sunlight or room lights for 48 hours after SONALA-001 administration
Hematologic toxicity:
Grade 4 neutropenia for more than 7 days Grade 3 or higher thrombocytopenia with clinically significant bleeding Neutropenic feverSafety and Tolerability of SONALA-001 SDT as assessed by the number of subjects with Adverse Events (AEs), adverse device effects (ADEs), serious AEs (SAEs) and serious device effects (SADEs) Day 1 to 12 months Safety and tolerability of SONALA-001 SDT
Definition of Adverse Event (AE) An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after the first dose of investigational drug. Abnormal laboratory values or test results occurring after the first dose of investigational drug constitute AEs only if they induce clinical signs or symptoms, are considered clinically significant, require therapy (e.g., hematologic abnormality that requires transfusion or hematological stem cell support) except electrolytes which require replacement therapy and correct to CTCAE grade ≤ 1 within 48 hours unless considered life-threatening, or require changes in study medication(s).Safety and Tolerability of SONALA-001 SDT as assessed by the number of subjects with abnormal hematology, chemistry, coagulation and urinalysis laboratory tests. Day 1 to 12 months Lab tests covered by CTCAE version 5.0 or most current will be graded accordingly. For lab tests covered by CTCAE, a Grade 0 will be assigned for all non-missing values not graded as 1 or higher. Grade 5 will not be used. For lab tests where grades are not defined by CTCAE, results will be categorized by low/normal/high classifications based on lab normal ranges or categorized by normal/abnormal for character (descriptive) lab values.
Progression-free survival rate at 6 Months (Phase 2) 6 Months To evaluate preliminary efficacy (PFS rate at 6 months) of the RP2D of ALA SDT treatments by mRANO in subjects with recurrent GBM
Safety of the RP2D of ALA SDT as assessed by the number of subjects with AEs/ADEs, SAEs/SADEs, abnormal laboratory tests, neurologic and physical examinations, vital signs, and ECGs. Day 1 to 12 months Safety of the RP2D of ALA SDT
- Secondary Outcome Measures
Name Time Method To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to infinity (AUC0-∞) (Phase 1) Day 1 to 24 hours post SONALA-001 dosing Samples will be collected at 12 time points during 24 hours pre/post SONALA-001 administration.
To evaluate preliminary efficacy and and OS (Phase 2) Up to 12 months OS, defined as time from first dose of study treatment to death due to any cause.
To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating Area Under the plasma Concentration (AUC) vs. time from time 0 to the last measurable time point (AUC-t) (Phase 1) Day 1 to 24 hours post SONALA-001 dosing Samples will be collected at 12 time points during 24 hours pre/post SONALA-001 administration.
To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to time to clearance. (Phase 1) Day 1 to 24 hours post SONALA-001 dosing Samples will be collected at 12 time points during 24 hours pre/post SONALA-001 administration.
To evaluate the preliminary antitumor activity Objective Response Rate (ORR): Complete Response (CR) and Partial Response (PR) by mRANO Day 1 to 12 months ORR defined as the proportion of subjects with a best overall response (BOR) of CR or PR as assessed per mRANO by investigator assessment
To evaluate preliminary efficacy and Time To Response (TTR) Up to 12 months TTR, calculated as time from first dose of study treatment to first documented objective response (CR or PR).
To evaluate preliminary efficacy and Progression Free Survival (PFS) Up to 12 months PFS defined as time from first dose of study treatment to progression or death due to any cause.
To evaluate preliminary efficacy and PFS rate at 6 and 12 months Up to 12 months PFS rate at 6 months (Phase 1) and 12 months defined as the percentage of subjects without progression or death at 6 months and 12 months.
To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to time to elimination rate constant. (Phase 1) Day 1 to 24 hours post SONALA-001 dosing Samples will be collected at 12 time points during 24 hours pre/post SONALA-001 administration.
To evaluate preliminary efficacy and Overall Survival (OS) (Phase 1) Up to 12 months OS, defined as time from first dose of study treatment to death due to any cause.
To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to time to maximum drug concentration (Tmax) (Phase 1) Day 1 to 24 hours post SONALA-001 dosing Samples will be collected at 12 time points during 24 hours pre/post SONALA-001 administration.
To evaluate the pharmacokinetics (PK) of ALA and Protoporphyrin IX (PpIX) following intravenous (IV) dosing with SONALA-001 by calculating AUC for plasma concentration vs. time from time 0 to time to terminal elimination half-life (t½) (Phase 1) Day 1 to 24 hours post SONALA-001 dosing Samples will be collected at 12 time points during 24 hours pre/post SONALA-001 administration.
To evaluate preliminary efficacy and Duration of Response (DOR) (Phase 1) Up to 12 months DOR, defined as time from date of first documented objective response (CR or PR) to the first documented progression or death due to any cause.
To evaluate preliminary efficacy and clinical benefit rate Clinical Benefit Rate (CBR) (Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Up to 12 months CBR defined as the proportion of subjects with a BOR of CR or PR or SD.
To evaluate preliminary efficacy and Duration of Clinical Benefit (DOCB) (Phase 2) Up to 12 months DOCB defined as time from date of first documented objective response (CR or PR) and SD to first documented progression or death due to any cause.
Trial Locations
- Locations (6)
NYU Langone Health
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Ivy Brain Tumor Center
🇺🇸Phoenix, Arizona, United States
UCSF
🇺🇸San Francisco, California, United States