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

• Sponsor: Michael Vogelbaum, MD, PhD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01575275
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 27
• Patients Per Site Per Month: 0.3

Study Details

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:

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

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

SECONDARY OBJECTIVES:

1. 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
• 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 1, 2012
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Aug 1, 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 [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 [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 [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 [From the date of surgery with aminolevulinic acid to the date of death, assessed up to 4 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Vogelbaum, MD, PhD, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01575275
• Other Study ID Numbers: CASE1311; NCI-2012-00452
• First Posted: Apr 11, 2012
• Last Update Posted: Jul 31, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Glioblastoma; Gliosarcoma; Aminolevulinic Acid

Study Results

Participant Flow

Arm/Group Title	Diagnostic (Aminolevulinic Acid)
Arm/Group Description	Patients receive aminolevulinic acid PO 2-4 hours before surgery. aminolevulinic acid: Given PO therapeutic conventional surgery: Undergo surgery
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Diagnostic (Aminolevulinic Acid)
Arm/Group Description	Patients receive aminolevulinic acid PO 2-4 hours before surgery. aminolevulinic acid: Given PO therapeutic conventional surgery: Undergo surgery
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 75%
>=65 years	2 25%
Sex: Female, Male (Count of Participants)
Female	1 12.5%
Male	7 87.5%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diagnostic (Aminolevulinic Acid)
Arm/Group Description	Patients receive aminolevulinic acid PO 2-4 hours before surgery. aminolevulinic acid: Given PO therapeutic conventional surgery: Undergo surgery
Measure Participants	8
Median (Full Range) [cc]	-0.342

2. Primary Outcome

Title	Comparison Between the Volume of Resected Tissue (Defined as the Volume of the Resection Cavity) and the Pre-operative Enhancing Tumor Volume
Description	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).
Time Frame	Up to day 1

Outcome Measure Data

Analysis Population Description

Outcome never analyzed. Study closed with the IRB in 2014

Arm/Group Title	Diagnostic (Aminolevulinic Acid)
Arm/Group Description	Patients receive aminolevulinic acid PO 2-4 hours before surgery. aminolevulinic acid: Given PO therapeutic conventional surgery: Undergo surgery
Measure Participants	0

3. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Outcome never analyzed. Closed with the IRB in 2014

Arm/Group Title	Diagnostic (Aminolevulinic Acid)
Arm/Group Description	Patients receive aminolevulinic acid PO 2-4 hours before surgery. aminolevulinic acid: Given PO therapeutic conventional surgery: Undergo surgery
Measure Participants	0

4. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diagnostic (Aminolevulinic Acid)
Arm/Group Description	Patients receive aminolevulinic acid PO 2-4 hours before surgery. aminolevulinic acid: Given PO therapeutic conventional surgery: Undergo surgery
Measure Participants	8
Median (Full Range) [months]	16

Adverse Events

Arm/Group Title	Diagnostic (Aminolevulinic Acid)
Arm/Group Description	Patients receive aminolevulinic acid PO 2-4 hours before surgery. aminolevulinic acid: Given PO therapeutic conventional surgery: Undergo surgery
All Cause Mortality
	Diagnostic (Aminolevulinic Acid)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Diagnostic (Aminolevulinic Acid)
	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)
Cardiac disorders
Syncope	1/8 (12.5%)	1
Nervous system disorders
Infection	1/8 (12.5%)	1
Vascular disorders
Thrombosis/embolism	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Diagnostic (Aminolevulinic Acid)
	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)
Blood and lymphatic system disorders
Anemia	2/8 (25%)	2
Lymphopenia	2/8 (25%)	2
Low Platelets	2/8 (25%)	2
General disorders
Pain	2/8 (25%)	6
Infections and infestations
Infection with unknown ANC - Meninges	1/8 (12.5%)	1
Investigations
hypoalbuminemia	2/8 (25%)	3
Hypocalcemia	1/8 (12.5%)	1
hyponatremia	1/8 (12.5%)	1
Nervous system disorders
Neuropathy: Sensory	1/8 (12.5%)	1
Syncope	1/8 (12.5%)	1
Renal and urinary disorders
Urinary Frequency	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction	1/8 (12.5%)	1
Vascular disorders
Thrombosis	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.