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Phase I Study of Orally Administered Aminolevulinic Acid for Resection of Malignant Astrocytomas

Primary Purpose

Astrocytoma, Glioma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
5-Aminolevulinic Acid
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Astrocytoma focused on measuring 5-ALA, Aminolevulinic Acid, Craniotomy, Brain Tumor, Surgical Resection, Neurosurgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have clinically documented primary brain tumor for which resection is clinically indicated. Radiographic findings should be consistent with high grade glioma. Intraoperative frozen section should either be: anaplastic astrocytoma (WHO Grade III astrocytoma) or glioblastoma (WHO Grade IV astrocytoma).
  • Patients must be aged greater than 18 years old
  • Karnofsky Performance Score > 70 (Appendix)

  • 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
    • AST/ALT within normal institutional limits
    • Creatinine within normal institutional limits

Exclusion Criteria:

  • Prior craniotomy for resection, deep seated tumors in thalamus and brain stem.
  • History of allergic reactions to compounds of similar chemical composition to ALA.
  • Personal or family history of porphyrias
  • Personal history of hepatitis or other liver diseases.
  • Pregnant women are excluded from this study because ALA is of unknown teratogenic 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 prior to treatment with ALA.
  • Inability to undergo magnetic resonance imaging (i.e. those patients with AICD/pacemakers).

Sites / Locations

  • Johns Hopkins Bayview Medical Center
  • Johns Hopkins Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

5-ALA

Arm Description

This arm will receive the investigational agent, 5-ALA.

Outcomes

Primary Outcome Measures

serious adverse event (SAE) Rate
It will be considered as a serious adverse event with possible, probable, and definitely attribution to 5-ALA (SAE, detailed in section 8) if (within 2 weeks of dosing): Grade 1 or 2 LFT abnormalities not resolving within 2 weeks A single documented Grade 3 or 4 LFT abnormalities A Grade 3 or 4 skin photosensitivity

Secondary Outcome Measures

Diagnostic Accuracy
The secondary objective of the study is to estimate sensitivity (true positive rate) and specificity (true negative rate); false positive rate and false negative rate; positive predict rate, and negative predict rate using a 5-ALA dose of 20 mg/kg to delineate tumor that may provide discrimination between normal and malignant tissue intra-operatively.

Full Information

First Posted
December 29, 2011
Last Updated
January 3, 2017
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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1. Study Identification

Unique Protocol Identification Number
NCT01502605
Brief Title
Phase I Study of Orally Administered Aminolevulinic Acid for Resection of Malignant Astrocytomas
Official Title
Phase I Study of Orally Administered Aminolevulinic Acid for Resection of Malignant Astrocytomas
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
PI leaving institution
Study Start Date
September 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This research is being done to study the safety and utility of 5-aminolevulinic acid (5-ALA) (also known as Gliolan) for identifying brain tumor tissue during surgery. The goal of this study is to determine if 5-ALA can differentiate between tumor and normal brain tissue. Sometimes, during brain surgery, the removal of tumor tissue can be difficult because the tumor can look like normal brain tissue. Studies in other countries have shown that in some brain tumors, 5-ALA can make the tumors appear brighter under ultraviolet light. This may make it easier for doctors to remove as much tumor as safely as possible from your brain. This study also hopes to see if 5-ALA can find different cell populations within the tumor that is removed and allow the researchers to better understand brain tumors. The purpose of this study is to: Find out how well 5-ALA can separate normal brain tissue from tumor tissues AND to see how well 5-ALA can find different cell populations within brain tumors Identify the amount of 5-ALA that should be taken before surgery to make the tumors glow under ultraviolet light Make sure the 5-ALA identifies tumor and not normal brain Make sure 5-ALA does not cause any side effects

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Astrocytoma, Glioma
Keywords
5-ALA, Aminolevulinic Acid, Craniotomy, Brain Tumor, Surgical Resection, Neurosurgery

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
5-ALA
Arm Type
Experimental
Arm Description
This arm will receive the investigational agent, 5-ALA.
Intervention Type
Drug
Intervention Name(s)
5-Aminolevulinic Acid
Intervention Description
A one time, single-dose administration of ALA is planned 4 hours pre-operatively the day of surgery. ALA will be mixed in the minimum volume of sterile water or juice immediately before use and given as a single oral bolus. Once ALA has been administered, patients will be kept in subdued lighting away from sunlight.
Primary Outcome Measure Information:
Title
serious adverse event (SAE) Rate
Description
It will be considered as a serious adverse event with possible, probable, and definitely attribution to 5-ALA (SAE, detailed in section 8) if (within 2 weeks of dosing): Grade 1 or 2 LFT abnormalities not resolving within 2 weeks A single documented Grade 3 or 4 LFT abnormalities A Grade 3 or 4 skin photosensitivity
Time Frame
2 weeks from dosing
Secondary Outcome Measure Information:
Title
Diagnostic Accuracy
Description
The secondary objective of the study is to estimate sensitivity (true positive rate) and specificity (true negative rate); false positive rate and false negative rate; positive predict rate, and negative predict rate using a 5-ALA dose of 20 mg/kg to delineate tumor that may provide discrimination between normal and malignant tissue intra-operatively.
Time Frame
72 hours post-operative

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have clinically documented primary brain tumor for which resection is clinically indicated. Radiographic findings should be consistent with high grade glioma. Intraoperative frozen section should either be: anaplastic astrocytoma (WHO Grade III astrocytoma) or glioblastoma (WHO Grade IV astrocytoma). Patients must be aged greater than 18 years old Karnofsky Performance Score > 70 (Appendix) 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 AST/ALT within normal institutional limits Creatinine within normal institutional limits Exclusion Criteria: Prior craniotomy for resection, deep seated tumors in thalamus and brain stem. History of allergic reactions to compounds of similar chemical composition to ALA. Personal or family history of porphyrias Personal history of hepatitis or other liver diseases. Pregnant women are excluded from this study because ALA is of unknown teratogenic 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 prior to treatment with ALA. Inability to undergo magnetic resonance imaging (i.e. those patients with AICD/pacemakers).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfredo Quinones, MD
Organizational Affiliation
Johns Hopkins School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

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Phase I Study of Orally Administered Aminolevulinic Acid for Resection of Malignant Astrocytomas

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