A Study of the Specificity and Sensitivity of 5- Aminolevulinic Acid (ALA) Fluorescence in Malignant Brain Tumors
This study is currently recruiting participants.
Verified February 2012 by Southern Illinois University
Sponsor:
Southern Illinois University
Collaborators:
Memorial Medical Center
DUSA Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Jeffrey W Cozzens, MD, Southern Illinois University
ClinicalTrials.gov Identifier:
NCT01128218
First received: May 13, 2010
Last updated: February 17, 2012
Last verified: February 2012
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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: 5-aminolevulinic acid |
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: | 6 |
| Study Start Date: | March 2011 |
| Estimated Study Completion Date: | June 2014 |
| Estimated Primary Completion Date: | June 2013 (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. Areas of the brain that are fluorescent and areas that are not fluorescent are evaluated for presence of tumor cells
|
Drug: 5-aminolevulinic acid
oral doses in phase 1 study of 10mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg and 50 mg/kg
Other Name: 5-ALA
|
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
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: Margaret MacGregor, MD | |
| Sub-Investigator: Brian K Russell, MD | |
Sponsors and Collaborators
Southern Illinois University
Memorial Medical Center
DUSA Pharmaceuticals, Inc.
Investigators
| Principal Investigator: | Jeffrey W Cozzens, MD | Southern Illinois University School of Medicine |
More Information
Additional Information:
Publications:
| Responsible Party: | Jeffrey W Cozzens, MD, Professor and Chair, 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: | February 17, 2012 |
| 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 Radiation-Sensitizing Agents Physiological Effects of Drugs Pharmacologic Actions Dermatologic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 21, 2013