Aminolevulinic Acid in Visualizing a Tumor During Surgery in Patients With Glioblastoma Multiforme

• ClinicalTrials.gov Identifier: NCT01575275
• Recruitment Status: Terminated
• First Posted: April 11, 2012
• Results First Posted: July 31, 2018
• Last Update Posted: July 31, 2018
• Sponsor: Michael Vogelbaum, MD, PhD
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Michael Vogelbaum, MD, PhD, Case Comprehensive Cancer Center

Study Description

Brief Summary:

The purpose of this study is to investigate the safety and performance of an investigational agent, known as 5-ALA or Gliolan (aminolevulinic acid), that many be useful to a surgeon for visualizing a tumor during surgery. It is also being studied to determine if there are differences in what Gliolan shows a surgeon compared to intraoperative magnetic resonance imaging (MRI)

Condition or disease	Intervention/treatment	Phase
Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor	Drug: aminolevulinic acid; Procedure: therapeutic conventional surgery	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the volume of residual enhancing tumor after a 5-ALA guided resection of a glioblastoma multiforme (GBM).

II. Determine the volume of tissue removed compared to the measured enhancing tumor evaluated on a pre-operative MRI.

SECONDARY OBJECTIVES:

I. Evaluate the time to tumor progression. II. Evaluate the overall survival.

OUTLINE:

Patients receive aminolevulinic acid orally (PO) 2-4 hours before surgery.

After completion of study treatment, patients are followed up for 2 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Phase 2 Comparative Study of 5-Aminolevulinic Acid (5-ALA) and Intraoperative MRI (iMRI) to Enhance Completeness of Resection of Glioblastoma
• Study Start Date: May 2012
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Diagnostic (aminolevulinic acid); Patients receive aminolevulinic acid PO 2-4 hours before surgery.	Drug: aminolevulinic acid; Given PO; Other Names: 5-ALA; 5-Aminolaevulinic Acid; ALA; Procedure: therapeutic conventional surgery; Undergo surgery

Outcome Measures

Primary Outcome Measures :

1. Change in Volume of Residual Enhancing Tumor, as Determined by Intraoperative Volume MRI at a Single Time Point Without and With Gadolinium, Following Maximal Resection With Use of Aminolevulinic Acid [ Time Frame: Day 1 ]
   Volume of enhancing tumor (initial and residual) will be determined by use of a softwarebased volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study).
2. Comparison Between the Volume of Resected Tissue (Defined as the Volume of the Resection Cavity) and the Pre-operative Enhancing Tumor Volume [ Time Frame: Up to day 1 ]
   Volume of enhancing tumor (initial and residual) will be determined by use of a software-based volumetric analysis method. Intra- and post-op definitions of residual tumor volume need to be adjusted for the presence of T1 hyperintensity due to signal from blood and blood products (as determined on pre-gadolinium volume study).

Secondary Outcome Measures :

1. Time to Disease Progression (TTP), Determined by Review of MRIs Performed Post Operatively as Clinically Indicated, Evaluated With Use of the New International Criteria Proposed by the Response in NeuroOncology (RANO) Committee [ Time Frame: From the date of surgery with aminolevulinic acid to the date of progression, assessed up to 1 year ]
2. Overall Survival, by Periodic Follow up Review of the Patient Charts and by Correlation With the Social Security Death Index [ Time Frame: From the date of surgery with aminolevulinic acid to the date of death, assessed up to 4 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients must have a suspected or biopsy proven newly diagnosed GBM, or a recurrent GBM or suspected GBM (in patient with pathologically diagnosed prior World Health Organization [WHO] grade II or III tumor) in a patient undergoing a clinically-indicated surgery.
• Age >= 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy is not a consideration for protocol entry
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Creatinine within normal institutional limits; OR
• Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document or have a parent or guardian with the ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

• Prior therapy is not an exclusion criterion
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to aminolevulinic acid (ALA)
• Current treatment with hypericin (or an extract) or other photosensitizing agents
• Personal or immediate family (parents, siblings, children) history of porphyrias
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ALA

Contacts and Locations

Locations

United States, Ohio

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Michael Vogelbaum, MD, PhD

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Vogelbaum, MD, PhD; Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

More Information

• Responsible Party: Michael Vogelbaum, MD, PhD, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01575275
• Other Study ID Numbers: CASE1311; NCI-2012-00452 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• First Posted: April 11, 2012
• Results First Posted: July 31, 2018
• Last Update Posted: July 31, 2018
• Last Verified: July 2018

Additional relevant MeSH terms:

Glioblastoma; Gliosarcoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Aminolevulinic Acid; Photosensitizing Agents; Dermatologic Agents