A Cancer Research UK Pharmacokinetic Study of BPA in Patients With High Grade Glioma to Optimize Uptake Parameters for Clinical Trials of BNCT
- To determine the optimal way to deliver boron phenylalanine (BPA) with or without
mannitol in terms of route (intravenous vs intraarterial), blood-brain barrier
disruption, and dose for use in subsequent therapeutic trials of boron neutron capture
therapy (BNCT) in patients with high-grade glioma.
- To evaluate the toxicity profile of BPA administered intravenously or intra-arterially.
- To evaluate the pharmacokinetic behavior of BPA using samples of blood, urine, tumor
tissue, normal brain tissue, extracellular fluid, and cerebrospinal fluid.
- To produce indicative treatment plans using BPA administered either intravenously or
intra-arterially with or without mannitol to support the design of combination studies
using BPA and thermal neutrons for BNCT.
- To evaluate the micro-distribution of boron resulting from the different routes of
administration using secondary ion mass spectroscopy (SIMS).
- To store surplus tissues removed during the trial for possible future studies.
OUTLINE: This is a dose-escalation study.
- Stage 1 (Route and Blood Brain Barrier Disruption [BBBD]): Patients receive one dose of
boron phenylalanine intravenously (IV) or intra-arterially (IA) over 2 hours. Some
patients may receive mannitol IA over 30 seconds before receiving boron phenylalanine.
Patients then undergo planned biopsy of the tumor. Some patients may then undergo
immediate surgical debulking of the tumor.
Boron distribution data is analyzed to determine the optimal administration schedule.
Patients in stage 2 receives boron phenylalanine via the optimal route established in stage
1. If addition of mannitol is found to be beneficial, then mannitol is used in stage 2
- Stage 2 (Dose-escalation): Patients receive 1 or 2 doses of boron phenylalanine IV or
IA (as determined in stage 1) over 2 hours on day 1. Patients may also receive mannitol
IA as in stage 1.
Tumor tissue, normal brain tissue, and cerebrospinal fluid are collected during biopsy
and/or surgery. Some patients undergo blood, urine, extracellular fluid sample collection
periodically for pharmacokinetic studies. Tumor tissue will be stored for future studies.
After completion of study treatment, patients are followed for 7 days and then once a month.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Masking: Open Label, Primary Purpose: Treatment
Optimal dose of boron phenylalanine (BPA)
University Hospital Birmingham
United Kingdom: Medicines and Healthcare Products Regulatory Agency