Study to Evaluate 5-ALA Combined With CV01 Delivery of Ultrasound in Recurrent High Grade Glioma

Alpheus Medical

Status and phase

Completed

Phase 1

Conditions

High Grade Glioma

Treatments

Device: CV01-delivered ultrasound

Drug: 5 Aminolevulinic Acid

Study type

Interventional

Funder types

Industry

Identifiers

NCT05362409

CV01-101

Details and patient eligibility

About

A Phase 1 Multi-center clinical Trial Evaluating the Safety and Tolerability of 5-aminolevulinic Acid (5-ALA) Combined With CV01 Delivery of Ultrasound for Sonodynamic Therapy (SDT) in Patients With recurrent High Grade Glioma (HGG).

Full description

High-grade gliomas are the most commonly occurring primary CNS tumors in adults. The investigational product in this clinical study is a drug-device combination product consisting of 5-ALA HCl oral solution and the CV01 ultrasound delivery device. 5-ALA will be administered as a sonosensitizer prior to CV01-delivered ultrasound and will be re-administered every 4 weeks prior to CV01 ultrasound delivery. The CV01 device will deliver non-ablative, low-intensity ultrasound to deep regions of the brain to induce apoptosis of cancer cells. Part A will focus on duration escalation and determining the recommended duration of CV01 delivered ultrasound. Part B will further explore safety and tolerability through cohort expansion at the recommended duration of CV01 delivered ultrasound. Part C will include an exploratory surgical cohort at the recommended duration of CV01 delivered ultrasound. This FIH study will evaluate escalating durations of ultrasound delivery with CV01 and will enroll up to 48 patients.

Enrollment

22 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria

Patient must provide informed consent, stating understanding of the procedures and investigational nature of the study treatment, and willingness to comply with study requirements
≥ 18 years of age
WHO performance status of ≤ 2 at screening
Part A: Previous histopathologically confirmed diagnosis of high-grade glioma and radiographic evidence of recurrence after prior therapy with radiotherapy. Eligible histologies include (according to WHO classification 2021):
1. Astrocytoma, WHO grade 3 and 4 (including subtypes)
2. Oligodendroglioma WHO grade 3 (including subtypes)
Parts B and C: Previous histopathologically confirmed diagnosis of glioblastoma and radiographic evidence of recurrence after prior therapy with radiotherapy. While Part A may include patients with any type of HGG and any number of recurrences, Parts B and C are restricted to patients with glioblastoma experiencing first recurrence.
Unifocal or multifocal tumor confined to the supratentorial compartment
Interval since last anti-cancer therapy relative to first 5-ALA treatment, as detailed below
1. End of radiotherapy >12 weeks (including skin-directed radiation for skin cancer),
2. Last cytotoxic chemotherapy (4 weeks, if prior nitrosureas 6 weeks).
3. Last biological therapy, i. If bevacizumab ≥ 6 weeks ii. If other monoclonal antibody, e.g., immune checkpoint inhibitor > 3 weeks iii. If tyrosine kinase inhibitor or other small molecule > 2 weeks
4. Any other investigational agent(s) ≥ 30 days or 5 half-lives, whichever is longer
5. Photodynamic therapy for skin cancer or actinic keratoses ≥ 12 weeks
Any toxicity attributable to prior anti-cancer therapy must be resolved to the patient's baseline level or ≤ Grade 1 (except alopecia).
Adequate bone marrow and organ function, defined by the following laboratory values:
1. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
2. Platelet count ≥ 100,000 cells/mm3
3. Hemoglobin (Hgb) ≥ 8 g/dL
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
5. Total bilirubin ≤ 1.5 x ULN (unless Gilbert's syndrome, then patients may be eligible if total serum bilirubin is ≤ 3.0 x ULN or direct bilirubin is ≤ 1.5 x ULN)
6. Creatinine clearance (CrCL) as estimated by Cockcroft-Gault equation of ≥ 50 mL/min
Adequate coagulation function defined as PT (prothrombin time)/PTT (partial thromboplastin time) within normal institutional values
Males or non-pregnant, non-lactating females who are postmenopausal, surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to study initiation or hysterectomy), or who agree to use effective contraceptive methods as defined by the protocol during the study and for 30 days after the last investigational treatment, see Postmenopausal is defined as at least 12 months natural spontaneous amenorrhea and a serum follicle stimulating hormone (FSH) concentration ≥ 40 IU/L, or at least 6 weeks following surgical menopause (bilateral oophorectomy).

a. Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test within 7 days prior to first 5-ALA administration
Agreement to adhere to Lifestyle Considerations throughout study duration
Part C, Surgical group only: Tumor resection surgery is clinically indicated and planned for the patient, regardless of study participation

Key Exclusion Criteria:

Primary infratentorial or brainstem tumors
Primary spinal cord tumors
Bihemispheric disease (enhancing or non-enhancing) or tumors that involve the bilateral corpus callosum
Women who are pregnant or breastfeeding
Inability to undergo MRI or receive gadolinium (Gd)-based contrast agents
Hypersensitivity to 5-ALA or porphyrins
Average skull thickness at the treatment field > 10 mm as assessed by Alpheus Medical.

The treatment field is defined as the various locations on the head where the transducer will be coupled to the patient. The average skull thickness at each treatment field will be determined by Alpheus Medical through post-processing the thin cut head computed tomography (CT) (without contrast). The patient's CT scan must be provided to Alpheus Medical for evaluation as part of the Screening and Enrollment process.
Hemorrhagic or ischemic stroke (including transient ischemic attacks) and central nervous system bleeding in the preceding 6 months that are not related to glioma surgery. History of prior intratumoral bleeding is not an exclusion criterion; however, patients with a history of prior intratumoral or intracranial bleeding will undergo a non-contrast head CT to exclude acute bleeding.
Patients who have clinically significant edema requiring urgent intervention (e.g., surgery, initiation of steroids, escalating doses of steroids).
Patients with progressive and rapid clinical deterioration that, in the opinion of the investigator, is likely to worsen during the first cycle of treatment or in the peri-operative interval (in the surgical cohort)
Cumulative prior RT dose > 64 Gy
Acute or chronic types of porphyria
Gastrointestinal disorder that negatively affects absorption
Known active hepatitis B or C (Note: testing is not required)
Known human immunodeficiency virus (HIV) infection (Note: testing is not required)
Unable to avoid phototoxic drugs (e.g., St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, and tetracyclines) for 24 hours prior to and following 5-ALA administration
Any other concurrent severe or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, cardiac disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)
Patient has a condition the Investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the patient at undue risk