Fluorescence-guided Surgery for Low- and High-grade Gliomas

NCT01502280 | Completed Phase 3

• 1 other identifier: IRB#10BN132
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

Gliomas are the most common primary brain tumor, yet remain a challenge to effectively treat. Mounting evidence suggests that survival improves with greater tumor removal, yet being able do a complete removal can be difficult due to the tumor's infiltrating nature. 5-aminolevulinic acid (5-ALA) is a natural compound that, when patients take it by mouth 3 hours before surgery, is selectively taken up by glioma cells and causes a red/pink fluorescence (glow) under a blue light that allows tumor margins to be seen during the course of surgery. While this compound is used as a standard-of-care agent in Europe, it remains under testing by the Food and Drug Administration (FDA). A recent clinical trial in Germany, however, has demonstrated a significant improvement in the rate of complete resection for certain brain tumors (65% vs. 34%). The Barrow 5-ALA Intraoperative Confocal (BALANCE) Trial will measure the effect of 5-ALA on the amount of glioma tumor removal. To improve the usefulness of 5-ALA, a new special microscope fitted with a blue light, will be used to magnify microscopic fluorescence at the tumor margins. The investigators' hypothesis is that 5-ALA fluorescence with the use of the special microscope during surgery will greatly lower the amount of tumor left behind.

Conditions

Glioma

Keywords

extent of resection; Glioma; 5-ALA; tumor fluorescence; confocal microscopy

Outcome Measures

Primary Outcomes (1)

• Volumetric extent of resection

  Volumetric analysis of MRI contrast T1-weighted images (for low grade gliomas) will be compared to the preoperative sequences to calculate the volume of residual disease. Slice-by-slice assessment of pre- and postoperative tumor volume will be quantified by sequentially measuring the area of tumor on each slice and then integrating the combined measurements. This methodology has been previously reported (Sanai et al., Journal of Neurosurgery, 2010; Sanai et al, The New England Journal of Medicine, 2008)

  Change in MRI from pre-operative to within 48 hours post-operative

Secondary Outcomes (3)

• Overall Survival rate(OS)

  Time from randomization until date of death assessed up to 48 months

• Progression-free survival rate (PFS)

  Time from randomization until first date of progression assessed up to 48 months

• National Institute of Health Stroke Scale (NIHSS)

  Change in score from pre-operative at post-operative, 6, 12, 18 and 24 months

Study Arms (2)

5-ALA/Gliolan® /5-Aminolevulinic acid

EXPERIMENTAL

Within 3 hours prior to surgery, patient will orally ingest \[or be given via Nasogastric (NG), Orogastric (OG), or Gastric tube (G-tube)\] 5-ALA/Gliolan®/5-Aminolevulinic acid mixed with sterile water (20mg/kg)

Drug: 5-Aminolevulinic acid (ALA)

Placebo - ascorbic acid

PLACEBO COMPARATOR

Within 3 hours prior to surgery, patient will orally ingest \[or be given via Nasogastric (NG), Orogastric (OG), or Gastric tube (G-tube)\] 1.5 Gm. placebo - ascorbic acid in 50 ml sterile water.

Drug: Placebo - ascorbic acid

Interventions

5-Aminolevulinic acid (ALA) DRUG

Following informed consent, within 3 hours prior to surgery, patient will orally ingest \[or be given via Nasogastric (NG), Orogastric (OG), or Gastric tube (G-tube)\] either (1) 5-ALA/Gliolan® mixed with sterile water (20mg/kg)

Also known as: 5-Aminolevulinic acid Hydrochloride, Gliolan®, 5-ALA

5-ALA/Gliolan® /5-Aminolevulinic acid

Placebo - ascorbic acid DRUG

Within 3 hours prior to surgery, patient will orally ingest \[or be given via Nasogastric (NG), Orogastric (OG), or Gastric tube (G-tube)\] 1.5 Gm. placebo - ascorbic acid in 50 ml sterile water.

Placebo - ascorbic acid

Eligibility Criteria

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

You may qualify if:

• Presumed newly-diagnosed supratentorial glioma (previous biopsy-only/no adjuvant therapy are eligible for randomization)
• Age \> 18 years
• Normal bone marrow function (WBC \> 3000, Platelets \> 100,000)

You may not qualify if:

• Infratentorial tumors
• Pregnancy
• Hypersensitivity to 5-aminolevulinic acid hydrochloride or porphyrins
• History of photosensitivity, porphyria, or exfoliative dermatitis
• Hepatic dysfunction in the last 12 months (defined by AST, ALT, ALP, bilirubin \> 2.5 x normal)
• Serum creatinine \> 180 µmol/L
• Estimated Glomerular Filtration Rate (eGFR) \< 60 ml/min/1.73m2
• Inability to undergo MRI scan with contrast

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead

Study Sites (1)

St. Joseph's Hospital and Medical Center/Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Related Publications (1)

• Sanai N, Snyder LA, Honea NJ, Coons SW, Eschbacher JM, Smith KA, Spetzler RF. Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas. J Neurosurg. 2011 Oct;115(4):740-8. doi: 10.3171/2011.6.JNS11252. Epub 2011 Jul 15.

  PMID: 21761971 RESULT

MeSH Terms

Conditions

Glioma

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nader Sanai, MD

  St. Joseph's Hospital Medical Center, Phoenix

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: December 30, 2011
• Study Start: November 1, 2010
• Primary Completion: January 1, 2018
• Study Completion: June 1, 2018
• Last Updated: November 24, 2023

Record last verified: 2017-01

Locations

US (1)