Aminolevulinic Acid During Surgery in Treating Patients With Malignant Brain Tumors

February 13, 2017 updated by: University of Washington

A Phase 1 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Malignant Glial Tumors of the Brain

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (photodynamic therapy)
Patients receive aminolevulinic acid PO 4 hours before undergoing surgery.
Other: laboratory biomarker analysis
Correlative studies
Drug: aminolevulinic acid
Given PO
Other Names:
  • 5-ALA
  • ALA
  • 5-Aminolaevulinic Acid
Procedure: therapeutic conventional surgery
Standard brain tumor surgery with intra-operative frameless MRI stereotactic guidance and intra-operative ultrasound guidance

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Establishment of a safe dose for oral ALA administration
Time Frame: For 30 days post-aminolevulinic acid dose
Using National Cancer Institute (NCI) Common Toxicity Criteria to quantify toxicity following ALA administration. We will use descriptive statistics to analyze the safety data, based on NCI toxicity criteria.
For 30 days post-aminolevulinic acid dose
Determination of which of 3 ALA doses provide optimal discrimination between normal and malignant tissue intraoperatively
Time Frame: During surgery and from samples collected during surgery
The results from three methods will be used collectively to determine whether or not it is prudent, safe and justified to proceed with 12 more patients using the highest dose tolerated without undue toxicity. The results from these three methods, both surgical fluorescence rating and neuropathologist ratings of fluorescence and presence, or absence, of tumor will be compared using a correlation coefficient.
During surgery and from samples collected during surgery

Secondary Outcome Measures

Outcome Measure
Time Frame
Comparison of time-to-progression (TTP) and survival to that in comparable cases performed without the aid of ALA
Time Frame: At week 5 and then every 8-12 weeks for 27 months
At week 5 and then every 8-12 weeks for 27 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Daniel Silbergeld, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

June 21, 2010

First Submitted That Met QC Criteria

June 21, 2010

First Posted (Estimate)

June 23, 2010

Study Record Updates

Last Update Posted (Actual)

February 15, 2017

Last Update Submitted That Met QC Criteria

February 13, 2017

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7140
  • NCI-2010-00946 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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