A Phase I/II Study to Evaluate Safety and Efficacy of the Boron Neutron Capture Therapy (BNCT) Using B10 L-BPA as Boron Carrier in Recurrent Meningioma
A Phase I/II Study to Evaluate Safety and Efficacy of the Boron Neutron Capture Therapy (BNCT) Using B10 L-BPA as Boron Carrier in Recurrent Meningioma
This Phase I/II study, titled 'A Study to Evaluate the Safety and Efficacy of Boron Neutron Capture Therapy (BNCT) Using B10 L-BPA as a Boron Carrier in Recurrent Meningioma', aims to assess the efficacy of B10 L-BPA with BNCT in patients with recurrent meningioma. The primary objective is to evaluate the safety and efficacy of BNCT with B10 L-BPA for recurrent meningioma treatment, using the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) as the standard for assessment.
Inclusion Criteria:
Age of 20 years and older.
Patients with recurrent intracranial meningioma confirmed by medical imaging, classified as WHO Grade 1 to 3 according to the World Health Organization grading system for meningioma, are eligible for inclusion.
Prior surgery, radiation therapy, radiosurgery, proton therapy, heavy ion therapy, or boron neutron capture therapy for the disease.
There must be a time interval ≥ 3 months between prior radiation therapy and the scheduled BNCT.
There must be a time interval ≥ 1 month between receipt of antitumor drugs and the scheduled BNCT.
Measurable disease by magnetic resonance imaging (MRI) and/or computed tomography (CT) scan and ≤ 12 cm in the longest dimension.
At least one measurable lesion that can be assessed by RECIST v1.1.
Eastern Cooperative Oncology Group (ECOG) Performance Score ≤ 2.
Life expectancy ≥ 3 months in the opinion of the investigator.
Adequate organ functions as defined below:
Hemoglobin ≥ 8.0 g/dL. White blood cell (WBC) count ≥ 2.5 x 10^9 /L. Neutrophil count ≥ 1.0 × 10^9/L. Platelet count ≥ 50 × 10^9/L. Aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN). Alanine aminotransferase (ALT) ≤ 2.5 × ULN. Serum creatinine ≤ 1.5 × ULN Estimated glomerular filtration rate(eGFR) >=15 mL / min / 1.73m2
Female subjects with reproductive potential must have a negative result of serum pregnancy test at the screening visit and urine pregnancy test before the B10 L-BPA administration.
Female subject with childbearing potential as well as male subject with reproductive potential must agree to refrain from unprotected sex and use 2 methods of highly effective contraception with their partner (e.g. barrier contraceptives [male condom, female condom, or diaphragm plus spermicide], intrauterine device, hormonal methods [hormone shot or injection, implants, combination oral contraceptives, or patches]) for ≥ 6 months after the BNCT until the end of this study.
Physically and mentally capable of participating in the study and willing to adhere to study procedures.
Provision of signed informed consent. -
Exclusion Criteria:
Patients who have an effective standard treatment option available.
Lymphoma or other tumor type that is expected to respond to cancer chemotherapy or to a dose of conventional radiation therapy that can be safely given.
History of malignancy other than meningioma within 5 years (except carcinoma in situ and non-melanoma skin cancer).
A time interval less than 3 months from previous radiation therapy for intracranial region.
Patients who had radiation myelitits or radiation necrosis of the brain/brain stem.
A time interval less than 3 months from last brain surgery and less than 1 month from previous chemotherapy.
Distant metastasis outside of skull.
Imaging studies demonstrating tumor invasion of the carotid artery.
Carotid blowout syndrome with active bleeding within 6 months.
The investigator will evaluate the subject's condition and determine whether to perform computed tomography angiography (CTA) to assess the health of the subject's vascular system. This evaluation will confirm whether the subject is suitable to participate in the trial.
Note: Subjects will be eligible for the study if they have undergone stent implantation and obtained consent from the investigator.
Active infections requiring systemic treatment.
Patients with severe congestive heart failure or renal failure, as well as myocardial infarction, unstable angina, or poorly controlled arrhythmia within 6 months prior to the scheduled BNCT.
Severe comorbidities including but not limited to poorly controlled epilepsy, poorly controlled diabetes mellitus, poorly controlled hypertension, chronic lung diseases, e.g., obstructive pneumonia, interstitial pneumonia, pulmonary fibrosis, and severe emphysema, kidney diseases, e.g., chronic renal failure, acute renal failure, phenylketonuria and nephrotic syndrome, cardiac diseases, e.g., New York Heart Association (NYHA) Functional Classification Class III or IV), phenylketonuria and/or other severe conditions in the opinion of the investigator.
Suspected or known hypersensitivity (including allergy) to any of the drug components or contrast media.
Subject with hereditary fructose intolerance.
With a cardiac pacemaker or an unremovable metal implant in the head and neck region that will interfere with MRI-based dose-planning or tumor response evaluation.
Restless subjects who are unable to lie or sit in a cast for 30-60 mins.
Any medical or psychiatric conditions that, in the opinion of the investigator, may interfere with optimal participation in the study or place the subject at increased risk of adverse events (AEs).
Concurrent systemic cancer treatments, such as chemotherapy, targeted therapy (including cetuximab or EGFR oral tyrosine kinase inhibitors), or immunotherapy.
History of substance or alcohol abuse within 6 months prior to the screening visit.
Female subject who is planning to be pregnant or lactating during the study period.
Subject who is considered unfit to participate in the clinical study as assessed by the investigator -