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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Southern Illinois University
Sponsor:
Collaborator:
DUSA Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Southern Illinois University
ClinicalTrials.gov Identifier:
NCT01128218
First received: May 13, 2010
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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. Time-to-progression, one year survival rate and total survival will be measured as a function of the extent of resection. (Details below in Detailed Description.)

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 Intervention Phase
Brain Neoplasms
Drug: Tumor fluorescence
Phase 1
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 1 and 2 Study of 5-aminolevulinic Acid (5-ALA) to Enhance Visualisation and Resection of Malignant Glial Tumors of the Brain

Resource links provided by NLM:


Further study details as provided by Southern Illinois University:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Change in the following factors will be continually reviewed between baseline and 6 months: nausea and vomiting; liver function; photo-sensitivity; survival


Secondary Outcome Measures:
  • Tumor fluorescence intra-operative assessment by neurosurgeon [ Time Frame: baseline ] [ Designated as safety issue: Yes ]
    During surgery, neurosurgeon will assess tumor fluorescence (0 to +++) in three distinct areas of fluorescence (Strong fluorescence, Weak fluorescence, No fluorescence) to determine level of 5-ALA mediated fluorescence.

  • Tumor fluorescence intra-operative assessment by neurosurgeon [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    During surgery, neurosurgeon will assess tumor fluorescence (0 to +++) in three distinct areas of fluorescence (Strong fluorescence, Weak fluorescence, No fluorescence) to determine level of 5-ALA mediated fluorescence.

  • Tumor density determined by post-operative imaging [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Tumor density from biopsies obtained by the neurosurgeon will be assessed by neuropathology (Solid tumor, Tumor mixed infiltrating normal brain, No tumor).

  • Tumor density determined by post-operative imaging [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Tumor density from biopsies obtained by the neurosurgeon will be assessed by neuropathology (Solid tumor, Tumor mixed infiltrating normal brain, No tumor).


Estimated Enrollment: 15
Study Start Date: March 2011
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tumor fluorescence
A single arm in this open-label study where all patients are treated with the study drug - 5-aminolevulinic acid. Areas of the brain that are fluorescent and areas that are not fluorescent are evaluated for presence of tumor cells
Drug: Tumor fluorescence
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
  • 5-aminolevulinic acid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 performance status <2 (Karnofsky >60%)
  • 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
  • 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
  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: NCT01128218

Contacts
Contact: Barbara C Lokaitis, BA, CCRP 217.545.9737 blokaitis@siumed.edu

Locations
United States, Illinois
Southern Illinois University School of Medicine Recruiting
Springfield, Illinois, United States, 62702
Contact: Barbara C Lokaitis, BA, CCRP    217-545-9737    blokaitis@siumed.edu   
Principal Investigator: Jeffrey W Cozzens, MD         
Sub-Investigator: Jose Espinosa, MD         
Sub-Investigator: Devin V Amin, MD, PhD         
Sponsors and Collaborators
Southern Illinois University
DUSA Pharmaceuticals, Inc.
Investigators
Principal Investigator: Jeffrey W Cozzens, MD Southern Illinois University School of Medicine
  More Information

Additional Information:
Cancer  This link exits the ClinicalTrials.gov site

Publications:
Responsible Party: Southern Illinois University
ClinicalTrials.gov Identifier: NCT01128218     History of Changes
Other Study ID Numbers: COZ-SIU 10-002-1
Study First Received: May 13, 2010
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Southern Illinois University:
Brain Neoplasms
5-ALA
Aminolevulinic acid
Fluorescence
Gliomas
Glioblastoma
Surgery

Additional relevant MeSH terms:
Brain Neoplasms
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
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014