Brain and Central Nervous System TumorsPhase 1NCT01233492
Boron Phenylalanine With or Without Mannitol in Treating Patients With Glioblastoma Multiforme
A Phase 1 study testing boron phenylalanine, mannitol and biologic sample preservation procedure in people with Brain and Central Nervous System Tumors, run by Cancer Research UK at 2 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- boron phenylalanine, mannitol and biologic sample preservation procedure
- Type of treatment
- Surgery or procedure
- How many people
- 36 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Oct 2007to Sep 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Radiologically and clinically suspected solitary glioblastoma multiforme
- High-grade disease
- Agreed to undergo stereotactic biopsy as part of routine diagnostic work-up
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- 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
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, England, B15 2TH
Cancer Research UK Clinical Trials Unit - Birmingham
Birmingham, England, B15 2TT
About this study
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
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.
Read the detailed description
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Tertiary
- 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
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- boron phenylalanine, mannitol, biologic sample preservation procedure, radiation therapy treatment planning/simulation
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
boron phenylalanineDrug
mannitolDrug
biologic sample preservation procedureOther
radiation therapy treatment planning/simulationRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal dose of boron phenylalanine (BPA)
Causality of each adverse event to BPA and grading severity according to NCI CTCAE Version 3.0
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
Secondary outcomes (3)
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
Change in the intra-nuclear percentage of 10B atoms in any cohort of the study of greater than 20%
Establishment of a repository of samples including serum and tumor tissue for future studies using techniques such as proteomics and DNA array
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2010 (estimated)
- Study startOct 2007
- Primary completionSep 2013
- Study completionSep 2013
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Garth Cruickshank, Principal investigator, University Hospital Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01233492
- Sponsor's protocol ID
- CDR0000687653
- Other IDs
- CRUK-PH1/093, EUDRACT-2004-002413-37
- Status last verified
- Oct 2013
- First submitted
- 2 Nov 2010
- Last updated
- 8 Oct 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01233492
- Acronym / sponsor ID
- CDR0000687653
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 3 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Tertiary
- 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
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| boron phenylalanine | Drug | – |
| mannitol | Drug | – |
| biologic sample preservation procedure | Other | – |
| radiation therapy treatment planning/simulation | Radiation | – |
Primary outcome
Optimal dose of boron phenylalanine (BPA)
Causality of each adverse event to BPA and grading severity according to NCI CTCAE Version 3.0
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
3 secondary outcomes
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
Change in the intra-nuclear percentage of 10B atoms in any cohort of the study of greater than 20%
Establishment of a repository of samples including serum and tumor tissue for future studies using techniques such as proteomics and DNA array
Results and safety
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Garth Cruickshank principal investigator
University Hospital Birmingham
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing boron phenylalanine, mannitol and biologic sample preservation procedure in people with Brain and Central Nervous System Tumors, run by Cancer Research UK at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal dose of boron phenylalanine (BPA). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2013.