| Eligibility |
Key Inclusion Criteria
1. Patient must provide informed consent, stating understanding of the procedures and
investigational nature of the study treatment, and willingness to comply with study
requirements
2. = 18 years of age
3. WHO performance status of = 2 at screening
4. 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.
5. Unifocal or multifocal tumor confined to the supratentorial compartment
6. 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
7. Any toxicity attributable to prior anti-cancer therapy must be resolved to the
patient's baseline level or = Grade 1 (except alopecia).
8. 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
9. Adequate coagulation function defined as PT (prothrombin time)/PTT (partial
thromboplastin time) within normal institutional values
10. 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
11. Agreement to adhere to Lifestyle Considerations throughout study duration
12. Part C, Surgical group only: Tumor resection surgery is clinically indicated and
planned for the patient, regardless of study participation
Key Exclusion Criteria:
1. Primary infratentorial or brainstem tumors
2. Primary spinal cord tumors
3. Bihemispheric disease (enhancing or non-enhancing) or tumors that involve the
bilateral corpus callosum
4. Women who are pregnant or breastfeeding
5. Inability to undergo MRI or receive gadolinium (Gd)-based contrast agents
6. Hypersensitivity to 5-ALA or porphyrins
7. 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.
8. 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.
9. Patients who have clinically significant edema requiring urgent intervention (e.g.,
surgery, initiation of steroids, escalating doses of steroids).
10. 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)
11. Cumulative prior RT dose > 64 Gy
12. Acute or chronic types of porphyria
13. Gastrointestinal disorder that negatively affects absorption
14. Known active hepatitis B or C (Note: testing is not required)
15. Known human immunodeficiency virus (HIV) infection (Note: testing is not required)
16. 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
17. 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)
18. 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
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