Boron Phenylalanine With or Without Mannitol in Treating Patients With Glioblastoma Multiforme

NCT ID: NCT01233492

Last Updated: 2013-10-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2013-09-30

Brief 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.

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

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

boron phenylalanine

Intervention Type: DRUG

mannitol

Intervention Type: DRUG

biologic sample preservation procedure

Intervention Type: OTHER

radiation therapy treatment planning/simulation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research UK

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Garth Cruickshank

Role: PRINCIPAL_INVESTIGATOR

University Hospital Birmingham

Locations

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, United Kingdom

Cancer Research UK Clinical Trials Unit - Birmingham

Birmingham, England, United Kingdom

Countries

United Kingdom

Other Identifiers

CRUK-PH1/093

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2004-002413-37

Identifier Type: -

Identifier Source: secondary_id

CDR0000687653

Identifier Type: -

Identifier Source: org_study_id