A Study of the Specificity and Sensitivity of 5- Aminolevulinic Acid (ALA) Fluorescence in Malignant Brain Tumors

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. Data collection will include measurement of dose-limiting toxicity, tumor fluorescence, and tumor density. Data analysis will evaluate toxicity, sensitivity, and specificity of 5-ALA. Following completion of the phase 1 portion of this trial, an additional 14 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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Patients must have clinically documented primary brain tumor for which resection is clinically indicated.
* 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 (Eastern Cooperative Oncology Group) performance status \<2 (Karnofsky \>60%)
* Normal organ and marrow function as defined below:

  * Leukocytes \> 3,000/mcL (microliter)
  * Absolute neutrophil count \> 1,500/mcL
  * Platelets \> 100,000/mcL
  * Total bilirubin within normal institutional limits AST (aspartate aminotransferase) (SGOT)/ALT (alanine transaminase) (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
* Agreement by women of child-bearing potential and men to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* 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

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• BACKGROUNDStummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. doi: 10.1016/S1470-2045(06)70665-9. PMID 16648043
• BACKGROUNDTonn JC, Stummer W. Fluorescence-guided resection of malignant gliomas using 5-aminolevulinic acid: practical use, risks, and pitfalls. Clin Neurosurg. 2008;55:20-6. No abstract available. PMID 19248665
• DERIVEDCozzens JW, Lokaitis BC, Delfino K, Hoeft A, Moore BE, Fifer AS, Amin DV, Espinosa JA, Jones BA, Acakpo-Satchivi L. A Phase 2 Sensitivity and Selectivity Study of High-Dose 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent Glioblastoma. Oper Neurosurg. 2024 Nov 11;29(1):71-79. doi: 10.1227/ons.0000000000001417. PMID 39526779