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

Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01502605
• Other study ID #: J1140
• Status: Terminated
• Phase: Phase 1
• First received: December 29, 2011
• Last updated: January 3, 2017
• Start date: September 2012
• Est. completion date: June 2016

Study information

• Verified date: January 2017
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: June 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Astrocytoma
• Glioma

Intervention

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.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No