Know Cancer

forgot password

A Cancer Research UK Pharmacokinetic Study of BPA in Patients With High Grade Glioma to Optimize Uptake Parameters for Clinical Trials of BNCT

Phase 1
45 Years
75 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

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

Inclusion Criteria


- Radiologically and clinically suspected solitary glioblastoma multiforme

- High-grade disease

- Agreed to undergo stereotactic biopsy as part of routine diagnostic work-up


- WHO performance status 0-2 (0-1 for patients ≥ 65 years old)

- Life expectancy > 4 months

- Hemoglobin ≥ 9.0 g/dL

- Neutrophil count ≥ 1.5 x 10^9/L

- Platelet count ≥ 100 x 10^9/L

- Serum bilirubin ≤ 1.5 times upper normal of limit (ULN)

- AST ≤ 1.5 times ULN

- Uncorrected EDTA-Isotope creatinine clearance ≥ 40 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use two forms of effective contraception 4 weeks prior to,
during, and for 6 months after completion of study therapy

- Able to cooperate with procedures and follow-up

- Not at high risk of complications from blood-brain barrier disruption with mannitol
on pre-treatment CT scan (an open quadrigeminal plate cistern, absence of dilatation
of the contralateral frontal horn, and absence of uncal herniation)

- No history of uncontrolled seizures

- No phenylketonuria

- No current or previous malignancies at sites other than the brain, except for
adequately treated cone-biopsied carcinoma in-situ of the uterine cervix or basal
cell or squamous cell carcinoma of the skin

- Not at high medical risk due to nonmalignant systemic disease, including active
uncontrolled infection

- No known hepatitis B, hepatitis C, or HIV positivity by serology

- No concurrent congestive heart failure, history of NYHA class III-IV cardiac disease,
history of myocardial infarction or active ischemic heart disease within the past
year, or history of cardiac arrhythmia or thromboembolic disease

- No other condition that, in the investigator's opinion, would not make the patient a
good candidate for the clinical trial


- At least 12 hours since prior and no concurrent steroids

- At least 48 hours since prior phenylalanine-containing drinks (e.g., colas)

- At least 48 hours since prior excessive consumption of phenylalanine-containing
foods, including any of the following:

- Low phenylalanine content (e.g., fruit juice, fruits [except bananas],
vegetables, and low-protein breads and pastas

- Medium phenylalanine content (e.g., corn, bread, french fries, potatoes, peas,
rice, and regular pasta)

- High phenylalanine content (e.g., refried beans, chicken, nuts, hamburgers,
peanuts, cheese, eggs, pork chops, steak, bananas, and milk)

- At least 4 weeks since prior major thoracic and/or abdominal surgery and recovered

- No prior cranial radiotherapy

- No prior endocrine therapy, immunotherapy, or chemotherapy for the brain tumor

- No other concurrent anticancer therapy or investigational drugs

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Optimal dose of boron phenylalanine (BPA)

Safety Issue:


Principal Investigator

Garth Cruickshank

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital Birmingham


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

October 2007

Completion Date:

September 2012

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms