Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors

University of Washington

Status and phase

Terminated

Phase 1

Conditions

Adult Anaplastic Oligodendroglioma

Recurrent Adult Brain Tumor

Adult Glioblastoma

Adult Anaplastic Astrocytoma

Adult Giant Cell Glioblastoma

Adult Mixed Glioma

Adult Gliosarcoma

Treatments

Drug: aminolevulinic acid

Procedure: therapeutic conventional surgery

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01148966

NCI-2010-00946 (Registry Identifier)

7140

Details and patient eligibility

About

This phase I trial is studying the side effects and best dose of aminolevulinic acid during surgery in treating patients with malignant brain tumors. Aminolevulinic acid becomes active when it is exposed to a certain kind of light and may help doctors find and remove tumor cells during surgery

Full description

PRIMARY OBJECTIVES I. Establish a safe dose for oral ALA administration.

SECONDARY OBJECTIVES I. Determine which of 3 ALA (aminolevulinic acid) doses (10, 20 or 30 mg/kg) provide optimal discrimination between normal and malignant tissue intraoperatively.

II. Determine whether or not the use of ALA (compared to comparable cases performed without the aid of ALA) leads to a higher rate of gross total resection, as determined by postoperative MRI scanning within 48 hour of surgery completion.

III. Compare time-to-progression and survival to that in comparable cases performed without the aid of ALA.

OUTLINE: This is a phase I, dose-escalation study

Patients receive aminolevulinic acid orally (PO) 4 hours before undergoing surgery. After completion of study treatment, patients are followed up at week 5 and then every 8-12 weeks for 27 months.

Enrollment

6 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients may have clinically documented primary malignant glioma for which re-resection is clinically indicated; in this instance, previous pathology slides will be reviewed by University of Washington Medical Center (UWMC) Neuropathology prior to surgery; alternatively, patients may have imaging studies (magnetic resonance imaging [MRI] and /or computed tomography [CT] scans), which are highly indicative of a new malignant glioma, for which surgical resection is clinically warranted; the anticipated histology at resection should include: glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma (mixed glioma)
Prior therapy is not a consideration in protocol entry; patients with recurrence of known malignant gliomas are eligible following UWMC neuropathology slide review
Eastern Cooperative Oncology Group (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/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,000/uL
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
The effects of ALA on the developing human fetus are unknown; 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
History of allergic reactions attributed to compounds of similar chemical or biologic composition to 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 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 ALA, breastfeeding should be discontinued if the mother is treated with ALA