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A Study of the Specificity and Sensitivity of 5-ALA Fluorescence in Malignant Brain Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00977795
Recruitment Status : Withdrawn (PI moving to Southern Illinois University to start new protocol)
First Posted : September 16, 2009
Last Update Posted : August 19, 2013
Information provided by (Responsible Party):
Jeffrey W. Cozzens, NorthShore University HealthSystem

Brief Summary:

Extent of resection is a very important prognostic factor affecting survival in individuals diagnosed with a malignant glioma. However, the infiltrative nature of the malignant glioma tumor cells produces indistinct borders between normal and malignant tissues, and the lack of easily identifiable tumor margins confounds attempts at total resection. The investigators propose to identify the borders of malignant gliomas intraoperatively using oral 5-aminolevulinic Acid (5-ALA) which results in fluorescence of the malignant cells and thereby provide an opportunity for more complete tumor resection.

When exogenous 5-ALA is provided at increased concentration the tumor cells will become fluorescent under ultraviolet light. This feature identifies the tumor cells intraoperatively and facilitates complete resection.

The following data will be collected:

  • Dose-limiting toxicity data
  • Tumor fluorescence assessed by neurosurgeon (0 to +++) in three distinct areas of fluorescence (Strong fluorescence, Weak fluorescence, No fluorescence)
  • Tumor density from biopsies obtained by the neurosurgeon in the same three distinct areas of fluorescence and assessed by neuropathology (Solid tumor, Tumor mixed infiltrating normal brain, No tumor)
  • Neurosurgeon's intra-operative estimate of residual tumor
  • Neuroradiologist's estimate of post-operative residual tumor on MRI
  • Time to progression by MRI
  • Survival (time to progression, one year survival rate and total survival

This trial will evaluate:

  • The toxicity of a single dose of oral 5-ALA given pre-operatively.
  • The sensitivity and specificity of 5-ALA - Protoporphyrin IX (Pp IX) as an intraoperative fluorescent detection agent and aid for resection of tumor tissue remaining in the walls of the resection cavity of primary and recurrent malignant brain tumors.
  • The relationship of the neurosurgeon's estimate of the extent of malignant glioma resection (as guided by tumor fluorescence) to the actual extent of resection determined by post-operative imaging.
  • The time-to-progression, one year survival rate and total survival as a function of the extent of resection.

Following completion of the phase 1 portion of this trial, an additional 15 subjects will be entered at the recommended phase 2 dose level in order to further define the above parameters at the recommended phase 2 dose level.

Condition or disease Intervention/treatment Phase
Brain Neoplasms Drug: 5-aminolevulinic acid Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 and 2 Study of 5-aminolevulinic Acid (5-ALA) to Enhance Visualisation and Resection of Malignant Glial Tumors of the Brain
Study Start Date : September 2009
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Arm Intervention/treatment
Experimental: Tumor fluorescence
A single arm in this open-label study where all patients are treated with the study drug. Areas of the brain that are fluorescent and areas that are not fluorescent are evaluated for presence of tumor cells
Drug: 5-aminolevulinic acid
oral doses in phase 1 study of 10mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg and 50 mg/kg
Other Names:
  • 5-ALA
  • aminolevulinic acid

Primary Outcome Measures :
  1. Establish a safe dose for oral 5-ALA administration. [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Determine the sensitivity and specificity of 5-ALA mediated fluorescence for malignant glioma tissue in the brain [ Time Frame: 24 months ]
  2. Compare the neurosurgeon's intra-operative estimate of the extent of malignant glioma resection (as guided by tumor fluorescence) with the actual extent of resection determined by post-operative imaging [ Time Frame: 24 months ]
  3. Compare time-to-progression and survival to that in comparable cases performed without the aid of 5-ALA [ Time Frame: 24 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have clinically documented primary brain tumor for which resection is clinically indicated. The anticipated histology at resection should include: Anaplastic astrocytoma (10002224), Astrocytoma malignant NOS (10003572), Brain stem glioma (10006143), Ependymoma (10014967), Ependymoma malignant (10014968), Glioblastoma (10018336), Glioblastoma multiforme (10018337), Gliosarcoma (10018340), Anaplastic oligodendroglioma (10026659), Oligodendroglioma (10030286), Medulloblastoma (10027107), Mixed astrocytoma-ependymoma (10027743), Miscellaneous CNS primary tumor (10007959), Supratentorial primitive neuroectodermal tumor (10056672)
  • Prior therapy is not a consideration in protocol entry
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of 5-ALA in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials
  • ECOG performance status <2 (Karnofsky >60%)
  • Life expectancy is not a consideration for protocol entry
  • Patients must have normal organ and marrow function as defined below:

    • Leukocytes > 3,000/mcL
    • Absolute neutrophil count > 1,500/mcL
    • Platelets > 100,000/mcL
    • Total bilirubin within normal institutional limits
    • AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal
    • Creatinine within normal institutional limits, OR
    • Creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • The effects of 5-ALA on the developing human fetus are unknown. 5-ALA has unknown teratogenic or abortifacient effects. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior therapy is not an exclusion criterion
  • Patients may not be receiving any other investigational agents at the time of entry into the study
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-ALA
  • Personal or family history of porphyrias
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because 5-ALA is of unknown teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 5-ALA, breastfeeding should be discontinued if the mother is treated with 5-ALA

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00977795

Sponsors and Collaborators
NorthShore University HealthSystem
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Principal Investigator: Jeffrey W. Cozzens, M.D. NorthShore University HealthSystem

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Responsible Party: Jeffrey W. Cozzens, Principle Investigator, NorthShore University HealthSystem Identifier: NCT00977795     History of Changes
Other Study ID Numbers: EH09-377
First Posted: September 16, 2009    Key Record Dates
Last Update Posted: August 19, 2013
Last Verified: August 2013

Keywords provided by Jeffrey W. Cozzens, NorthShore University HealthSystem:
Brain Neoplasms
Aminolevulinic acid

Additional relevant MeSH terms:
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Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Aminolevulinic Acid
Photosensitizing Agents
Dermatologic Agents