More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

A Multicenter Phase II Study of 5-Aminolevulinic Acid (ALA) to Enhance Visualization and Resection of Newly Diagnosed or Recurrent Malignant Gliomas

The purpose of this study is to determine the safety and utility of 5-aminolevulinic acid (ALA) for identifying your tumor during surgery. 5-ALA is not FDA approved at this time. When the investigators remove the tumor from your brain, it is important that they remove all of the tumor and not remove parts of normal brain. Sometimes this can be difficult because the tumor can look like normal brain. In some brain tumors, 5-ALA can make the tumors glow red under blue light. This may make it easier for your doctor to take out all of the tumor from your brain. The purpose of this study is to:

• Make sure that 5-ALA helps the doctor remove more of the tumor.
• Make sure 5-ALA does not cause any side effects.

If you do not want to participate in this study, your doctor(s) will still do their best to remove all of the tumor in your brain. Whether or not you join this study will not change your treatment for your brain tumor.

Study Overview

• Status: Withdrawn
• Conditions: Glioblastoma; Brain Cancer; Brain Tumors; Brain Tumor, Recurrent; Benign Neoplasms, Brain; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas
• Intervention / Treatment: Drug: 5-ALA (Gliolan)

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30322
      • Emory University Winship Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have a clinically documented primary brain tumor for which resection is clinically indicated. Individuals with suspected newly diagnosed or recurrent malignant gliomas will be considered eligible for the study. The anticipated histology at resection should include: Anaplastic astrocytoma (10002224), Anaplastic ependymoma, Anaplastic oligodendroglioma, Astrocytoma malignant NOS (10003572), Glioblastoma (10018336), Glioblastoma multiforme (10018337), or Gliosarcoma (10018340).
• Prior therapy is not a consideration in protocol entry.
• Age 18-80.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%).
• Life expectancy is not a consideration for protocol entry.

• Subjects must have normal organ and marrow function as defined below:

  • Leukocytes ≥ 3,000/mL
  • Platelets ≥ 100,000/mL
  • Total bilirubin below upper limit of normal
  • Aspartate aminotransferase (AST) (SGOT)/alanine aminotransferase (ALT) (SGPT) ≤ 2.5 X institutional upper limit of normal
  • Creatinine below upper limit of normal OR
  • Creatinine clearance ≥ 60 mL/min/1.73 m² for patients with creatinine levels above institutional normal
• The effects of aminolevulinic acid (ALA) on the developing human fetus are unknown. For this reason, 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. A pregnancy test will be performed for all women of childbearing ability prior to surgery. Women who are pregnant will be excluded from the trial.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Tumors of or involving the midline, basal ganglia, or brain stem as assessed by MRI.
• Subjects may not be receiving any experimental therapies.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to aminolevulinic acid (ALA). Patients should refrain from use of other potential phototoxic substances (e.g. tetracyclines, sulfonamides,fluoroquinolones, hypericin extracts) for 72 hours.
• Personal or family 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 because aminolevulinic acid (ALA) is of unknown teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with aminolevulinic acid (ALA), breastfeeding should be discontinued if the mother is treated with aminolevulinic acid (ALA).
• Women who are pregnant will be excluded from the trial.
• Prior history of GI perforation, diverticulitis, and/or peptic ulcer disease.
• Inclusion of women and minorities: both men and women and members of all ethnic groups are eligible for this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5-ALA (Gliolan); Fluorescent substance to help visualize and remove as much tumor as possible without harming healthy tissue.	Drug: 5-ALA (Gliolan); 20 mg/kg administered once 3-5 hours prior to surgery; Other Names: 5-ALA; Aminolevulinic acid; Gliolan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Radicality of Brain Tumor Resection	Within the first 48 hours after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival every 3 months after surgery	Every 3 months until tumor progression on MRI

Collaborators and Investigators

• Sponsor: Constantinos Hadjipanayis
• Collaborators: National Cancer Institute (NCI); NX PharmaGen
• Investigators: Principal Investigator: Costas Hadjipanayis, MD, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): September 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimate): October 4, 2011

Study Record Updates

• Last Update Posted (Estimate): May 17, 2016
• Last Update Submitted That Met QC Criteria: May 13, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Surgery; 5-ALA; Brain Tumors; Glioblastoma; Brain Cancer; Fluorescence; Benign Neoplasms, Brain; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Aminolevulinic acid
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Glioblastoma; Recurrence; Glioma; Brain Neoplasms; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: GCO 15-2034; WCI1999-11 (Other Identifier: Other); R01CA176659 (U.S. NIH Grant/Contract); R21CA186169 (U.S. NIH Grant/Contract); IRB00051663 (Other Identifier: Emory University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No