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

Phase 1

Terminated

• Conditions: Astrocytoma; Glioma
• Interventions: Drug: 5-Aminolevulinic Acid

• Registration Number: NCT01502605
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-12-29
• Study First Submitted QC: 2011-12-29
• Study First Posted: 2011-12-30
• Study Start: 2012-09
• Primary Completion: 2015-05
• Study Completion: 2016-06
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-03
• Last Update Posted: 2017-01-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
5-ALA	5-Aminolevulinic Acid	This arm will receive the investigational agent, 5-ALA.

Primary Outcome Measures

Name	Time	Method
serious adverse event (SAE) Rate	2 weeks from dosing	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

Name	Time	Method
Diagnostic Accuracy	72 hours post-operative	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.

Trial Locations

Locations (2)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins Bayview Medical Center; 🇺🇸 Baltimore, Maryland, United States