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

NCT01233492 | Terminated Phase 1

• 3 other identifiers: CDR0000687653CRUK-PH1/093EUDRACT-2004-002413-37
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (3)

• 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

Interventions

boron phenylalanine DRUG

mannitol DRUG

biologic sample preservation procedure OTHER

radiation therapy treatment planning/simulation RADIATION

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (2)

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, B15 2TH, United Kingdom

Location

Cancer Research UK Clinical Trials Unit - Birmingham

Birmingham, England, B15 2TT, United Kingdom

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Mannitol

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Garth Cruickshank

  University Hospital Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2010
• First Posted: November 3, 2010
• Study Start: October 1, 2007
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: October 8, 2013

Record last verified: 2013-10

Locations

GB (2)