Fluorescence-guided Surgery for Low- and High-grade Gliomas (BALANCE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by St. Joseph's Hospital and Medical Center, Phoenix
Sponsor:
Information provided by (Responsible Party):
St. Joseph's Hospital and Medical Center, Phoenix
ClinicalTrials.gov Identifier:
NCT01502280
First received: December 22, 2011
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Glioma
Drug: 5-Aminolevulinic acid (ALA)
Drug: Placebo - ascorbic acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Barrow 5-ALA Intraoperative Confocal Evaluation Trial

Resource links provided by NLM:


Further study details as provided by St. Joseph's Hospital and Medical Center, Phoenix:

Primary Outcome Measures:
  • Volumetric extent of resection [ Time Frame: Change in MRI from pre-operative to within 48 hours post-operative ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • Overall Survival rate(OS) [ Time Frame: Time from randomization until date of death assessed up to 48 months ] [ Designated as safety issue: No ]
  • Progression-free survival rate (PFS) [ Time Frame: Time from randomization until first date of progression assessed up to 48 months ] [ Designated as safety issue: No ]
  • National Institute of Health Stroke Scale (NIHSS) [ Time Frame: Change in score from pre-operative at post-operative, 6, 12, 18 and 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 192
Study Start Date: November 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5-ALA/Gliolan® /5-Aminolevulinic acid
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)
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)
Other Names:
  • 5-Aminolevulinic acid Hydrochloride
  • Gliolan®
  • 5-ALA
Placebo Comparator: Placebo - ascorbic acid
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
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.

Detailed Description:

Gliomas are the most common primary brain tumor, yet are associated with a 12-14 month overall survival in the United States. Mounting evidence suggests that survival improves with greater extent of resection, yet achieving a complete radiographic resection is challenging due to the tumor's infiltrating nature. Oral 5-aminolevulinic acid (5-ALA/Gliolan®) is a natural compound that, when administered to patients within 3 hours prior to surgery, is selectively metabolized by glioma cells and induces a red/pink fluorescence under blue light that facilitates intraoperative identification of tumor margins. While this compound is used as a standard-of-care agent in Europe, it remains under examination by the Food and Drug Administration (FDA). A recent multicenter randomized, single-blind, controlled study in Germany demonstrated a significant improvement in the rate of complete resection for high-grade gliomas, as compared to conventional microneurosurgery (65% vs. 34%) (Stummer et al., Lancet Oncology 2006).

Patients with presumed newly-diagnosed glioma will be entered into the trial. On the basis of their expected extent of resection (low vs. high), they will be stratified in one of 2 groups - Group 1 (expected high extent or resection) or Group 2 (expected low extent of resection). Following stratification, patients with newly-diagnosed disease will be randomized to receive either study drug (5-ALA/Gliolan®) or placebo (ascorbic acid) prior to surgery. Those who have had previous biopsy only without further treatment will be eligible for randomization. Intraoperatively, 5-ALA/Gliolan® patients will undergo resection with combined fluorescence microscopy and confocal microscopy. Placebo patients will undergo resection with standard light microscopy. Postoperatively, patients will have an MRI scan with and without contrast within 48 hours of surgery. Subsequent analysis of each patient will include assessment of the primary endpoint, that is,volume of residual disease (VRD) by volumetrically quantifying the tumor before and after surgery using T1-weighted contrast-enhancement (high-grade gliomas) or T2-weighted hyperintensity (low-grade gliomas). Similarly, volumetric extent of resection will also be measured. Other secondary endpoints will include overall survival (OS), progression-free survival (PFS), and National Institute of Health Stroke Scale (NIHSS) (collected at baseline, 7-10 days post-op and at 6, 12, 18, and 24 months post op).

The Barrow 5-ALA Intraoperative Confocal (BALANCE) study will quantify the impact of 5-ALA/Gliolan(R) on low- and high-grade glioma extent of resection. To enhance the efficacy of 5-ALA/Gliolan(R), particularly for low-grade gliomas that fluoresce less vigorously due to their comparatively lower cellular metabolism, intraoperative confocal microscopy will be used to amplify microscopic fluorescence at the tumor margins. The investigators' hypothesis is that, for both low- and high-grade gliomas, 5-ALA/Gliolan(R) fluorescence in conjunction with intraoperative confocal microscopy will significantly lower the VRD.

Goals:

1. To determine the impact of intraoperative fluorescence and confocal microscopy on the volume of residual disease following resection of a newly-diagnosed glioma.

Sub-goals:

  1. To assess the feasibility and utility of combining intraoperative fluorescence with confocal microscopy.
  2. To determine the impact of this combined approach in improving volumetric extent of resection.
  3. To determine the impact of this combined approach in improving overall survival and 6-month progression-free survival.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01502280

Contacts
Contact: Norissa Honea, RN, PhD 602-406-6267 Norissa.Honea@dignityhealth.org

Locations
United States, Arizona
St. Joseph's Hospital and Medical Center/Barrow Neurological Institute Recruiting
Phoenix, Arizona, United States, 85013
Contact: Norissa Honea, RN, PhD    602-406-6267    Norissa.Honea@dignityhealth.org   
Principal Investigator: Nader Sanai, MD         
Sub-Investigator: William White, MD         
Sub-Investigator: Peter Nakaji, MD         
Sub-Investigator: Randall Porter, MD         
Sub-Investigator: Taro Kaibara, MD         
Sub-Investigator: Kris Smith, MD         
Sub-Investigator: Mark Garrett, MD         
Sub-Investigator: Andrew Little, MD         
Sub-Investigator: John Wanebo, MD         
Sub-Investigator: Steve Chang, MD         
Sponsors and Collaborators
St. Joseph's Hospital and Medical Center, Phoenix
Investigators
Principal Investigator: Nader Sanai, MD St. Joseph's Hospital Medical Center, Phoenix
  More Information

No publications provided

Responsible Party: St. Joseph's Hospital and Medical Center, Phoenix
ClinicalTrials.gov Identifier: NCT01502280     History of Changes
Other Study ID Numbers: IRB#10BN132
Study First Received: December 22, 2011
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Joseph's Hospital and Medical Center, Phoenix:
extent of resection
Glioma
5-ALA
tumor fluorescence
confocal microscopy

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aminolevulinic Acid
Ascorbic Acid
Photosensitizing Agents
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 21, 2014