Safety Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Malignant Tumors of the Brain

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
Mitchel Berger, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01116661
First received: May 3, 2010
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

The prodrug, 5-Aminolevulinic acid (ALA), has been shown to lead to intracellular accumulation of fluorescent porphyrins in high grade malignant gliomas in the brain. On imaging, this accumulation of fluorescent porphyrins helps delineate tumor borders, resulting in the surgeon being better able to visualize and thus able to make a complete, or near-complete resection of the tumor.


Condition Intervention Phase
Glioma
Drug: 5-Aminolevuline Acid
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Malignant Tumors of the Brain

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • To determine if the use of 5-aminolevulinic acid (ALA) helps distinguish tumor cells [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    To determine if the use of 5-aminolevulinic acid (ALA) helps distinguish tumor cells from normal cells leading to an increase in the amount of tumor removal during neurosurgical resection of malignant glioma.


Secondary Outcome Measures:
  • Determine the safety of 5-aminolevulinic acid (ALA) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Determine the safety of a single dose of 5-aminolevulinic acid (ALA) administered preoperatively at a dose of 20 mg/kg body weight.


Estimated Enrollment: 200
Study Start Date: August 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALA Drug: 5-Aminolevuline Acid
Given orally at a dose of 20 mg/kg body weight 3hrs before anesthesia prior to surgery

Detailed Description:

The drug, 5-aminolevulinic acid (ALA), which leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas will be used under investigation for identification and resection of high grade gliomas. Surgery will be done using a modified neurosurgical microscope, with a fluorescent kit that enables switching from the conventional white light to a violet-blue excitation light for visualization during tumor resection. If deemed safe by the neurosurgeon, any area of the resection bed determined to be fluorescence-positive for tumor will be removed with appropriate designation of tissue for histopathological evaluation. After this resection, additional fluorescence images will be obtained and the process repeated until the image is negative for tumor. At all times, the decision to resect will be limited by clinical judgment of safety.

The desire is that a more complete resection will occur due to the surgeon's ability to better visualize and distinguish between tumor and normal tissue, and thus be able to remove as much, or most of, the tumorous tissue, resulting in a better outcome for the patient, or for future patients.

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Presumptive diagnosis of high grade glioma based on imaging studies, or will have recurrent high-grade gliomas that have previously undergone diagnosis (astrocytoma, oligodendroglioma, mixed oligo-astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme). Both of these groups will be undergoing craniotomy for tumor resection.
  2. Patient age 18 to 72 years.
  3. Karnofsky performance of 60% or greater
  4. Patients must have normal organ and marrow function as defined below:

    Leukocytes >3,000/μL Absolute neutrophil count >1,500/μL Platelets >100,000/μL 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.

  5. The effects of Aminolevulinic Acid (ALA) on the developing human fetus are unknown. Therefore, 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.
  6. Patient must have the ability to understand and the willingness to sign a written informed consent document or have a parent or guardian with the ability to understand and the willingness to sign the written informed consent.

Exclusion Criteria:

  1. Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA).
  2. Subjects with a history or family history of Porphyrias
  3. Subjects with 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.
  4. Pregnancy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01116661

Contacts
Contact: Silvia Gonzalez, BS 415-353-2523 gonzalezsj@neurosurg.ucsf.edu
Contact: Valerie A Kivett, BS 415-353-2076 Kivettv@neurosurg.ucsf.edu

Locations
United States, California
UCSF Department of Neurosurgery Recruiting
San Francisco, California, United States, 94143
Contact: Silvia Gonzalez, BS    415-353-2523    gonzalezsj@neurosurg.ucsf.edu   
Contact: Valerie A Kivett, BS    415-353-2076    kivettv@neurosurg.ucsf.edu   
Principal Investigator: Mitchel S Berger, MD         
Sub-Investigator: Michael Prados, MD         
Sub-Investigator: Susan S Chang, MD         
Sub-Investigator: Nicholas Butowski, MD         
Sub-Investigator: Jennifer Clarke, MD, MPH         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Mitchel S Berger, MD UCSF Department of Neurosurgery
  More Information

No publications provided

Responsible Party: Mitchel Berger, MD, Chairman, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01116661     History of Changes
Other Study ID Numbers: 10101
Study First Received: May 3, 2010
Last Updated: October 25, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
glioma
malignant high grade glioma

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aminolevulinic Acid
Photosensitizing Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014