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

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

Study Overview

• Status: Terminated
• Conditions: Glioma; Astrocytoma
• Intervention / Treatment: Drug: 5-Aminolevulinic Acid

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

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 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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5-ALA; This arm will receive the investigational agent, 5-ALA.	Drug: 5-Aminolevulinic Acid; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2 weeks from dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	72 hours post-operative

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Alfredo Quinones, MD, Johns Hopkins School of Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: December 29, 2011
• First Submitted That Met QC Criteria: December 29, 2011
• First Posted (Estimate): December 30, 2011

Study Record Updates

• Last Update Posted (Estimate): January 5, 2017
• Last Update Submitted That Met QC Criteria: January 3, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Brain Tumor; Aminolevulinic Acid; 5-ALA; Surgical Resection; Neurosurgery; Craniotomy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Astrocytoma; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: J1140