Boron Phenylalanine With or Without Mannitol in Treating Patients With Glioblastoma Multiforme
RATIONALE: Giving boron phenylalanine in different ways and measuring it in tissue in patients with glioblastoma multiforme may help in planning better radiation therapy, such as boron neutron capture therapy, for patients in the future.
PURPOSE: This phase I trial is studying the side effects, best dose boron phenylalanine, and best way of giving it with or without mannitol in treating patients with glioblastoma multiforme.
Brain and Central Nervous System Tumors
Drug: boron phenylalanine
Other: biologic sample preservation procedure
Radiation: radiation therapy treatment planning/simulation
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Cancer Research UK Pharmacokinetic Study of BPA in Patients With High Grade Glioma to Optimize Uptake Parameters for Clinical Trials of BNCT|
- Optimal dose of boron phenylalanine (BPA) [ Designated as safety issue: No ]
- Causality of each adverse event to BPA and grading severity according to NCI CTCAE Version 3.0 [ Designated as safety issue: Yes ]
- Pharmacokinetic (PK) parameters used to construct a PK model with the aim of being able to predict boron up-take by tumor and normal brain tissue [ Designated as safety issue: No ]
- Change in mean dose to the planning target volume of greater than 15%, for a constant maximum and mean dose to normal tissue in any treatment cohort of the study [ Designated as safety issue: No ]
- Change in the intra-nuclear percentage of 10B atoms in any cohort of the study of greater than 20% [ Designated as safety issue: No ]
- Establishment of a repository of samples including serum and tumor tissue for future studies using techniques such as proteomics and DNA array [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01233492
|Cancer Research UK Clinical Trials Unit - Birmingham|
|Birmingham, England, United Kingdom, B15 2TT|
|Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust|
|Birmingham, England, United Kingdom, B15 2TH|
|Principal Investigator:||Garth Cruickshank||University Hospital Birmingham|