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

NCT01502605 | Terminated Phase 1 DMC

• 1 other identifier: J1140
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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

Conditions

Astrocytoma; Glioma

Keywords

5-ALA; Aminolevulinic Acid; Craniotomy; Brain Tumor; Surgical Resection; Neurosurgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Diagnostic Accuracy

  72 hours post-operative

Study Arms (1)

5-ALA

EXPERIMENTAL

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

Drug: 5-Aminolevulinic Acid

Interventions

5-Aminolevulinic Acid DRUG

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.

5-ALA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (2)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Astrocytoma; Glioma; Brain Neoplasms

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Alfredo Quinones, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2011
• First Posted: December 30, 2011
• Study Start: September 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2016
• Last Updated: January 5, 2017

Record last verified: 2017-01

Locations

US (2)