Imaging Procedure Using ALA in Finding Residual Tumor in Grade IV Malignant Astrocytoma

NCT00752323 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CASE1305
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Imaging procedures that use aminolevulinic acid (ALA) may help find and diagnose residual tumor in participants with grade IV malignant astrocytoma who are undergoing surgery to remove the tumor. PURPOSE: Our primary long-term goal is to improve the completeness of surgical resection of malignant brain tumor through image- guided fluorescence localization. We hypothesize that the use of qualitative fluorescence imaging and point PpIX concentration quantification will enable more complete tumor resection than normal direct (i.e., white light) visualization, and thereby improve participant survival.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma; recurrent adult brain tumor

Outcome Measures

Primary Outcomes (1)

• Assess 2 doses of 5-ALA

  This clinical trial has ALA dose at 2 levels (10 and 20 mg/kg) and ALA administration time at 1 time point (6h). During surgery, the intraoperative fluorescence observations and PpIX concentration measurements will be taken by the surgeon. The second part of each biopsy will have the PpIX concentration determined.

  6 hours before midpoint of surgery

Secondary Outcomes (2)

• Correlation between intensity of in vivo fluorescence and the pathologist's quantification of tumor in biopsy specimens (e.g., percentage of tumor present) as measured by PpIX concentration and intra-operative fluorescence intensity

  Quantitative fluorescence imaging of tumor tissue and normal tissue at approximately the midpoint of surgery and then after maximal resection of the tumor.

• Correlation between the amount and location of residual tumor detected intraoperatively by fluorescence imaging and frameless stereotaxy after maximal resection and the post-operative image enhancement on CT scan and/or MRI

  Tumor tissue samples are obtained at the same two timepoints (the midpoint of surgery and then after maximal resection of the tumor)

Study Arms (4)

Arm I: Newly diagnosed GBM 10mg/kg

EXPERIMENTAL

Arm I: Newly diagnosed GBM patients receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery.

Drug: aminolevulinic acid; Procedure: Surgical Resection

Arm II: Newly diagnosed GBM 20mg/kg

EXPERIMENTAL

Arm II: Newly diagnosed GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.

Drug: aminolevulinic acid; Procedure: Surgical Resection

Arm III: Recurrent GBM 10mg/kg

EXPERIMENTAL

Arm III: Recurrent GBM patients receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery.

Drug: aminolevulinic acid; Procedure: Surgical Resection

Arm IV: Recurrent GBM 20mg/kg

EXPERIMENTAL

Arm IV: Recurrent GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.

Drug: aminolevulinic acid; Procedure: Surgical Resection

Interventions

aminolevulinic acid DRUG

Given orally

Also known as: δ-Aminolevulinic acid Hydrochloride, 5-Amino-4-oxopentanoic acid Hydrochloride, 5-Aminolaevulinic acid Hydrochloride

Arm I: Newly diagnosed GBM 10mg/kg; Arm II: Newly diagnosed GBM 20mg/kg; Arm III: Recurrent GBM 10mg/kg; Arm IV: Recurrent GBM 20mg/kg

Surgical Resection PROCEDURE

Surgical resection - 6 biopsies from 3 fluorescent regions

Arm I: Newly diagnosed GBM 10mg/kg; Arm II: Newly diagnosed GBM 20mg/kg; Arm III: Recurrent GBM 10mg/kg; Arm IV: Recurrent GBM 20mg/kg

Eligibility Criteria

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

You may qualify if:

• Tumor Pathology: Newly diagnosed or recurrent malignant gliomas WHO grade IV
• Location: Supratentorial
• Resection: Tumor must be judged suitable for resection on the basis of imaging studies.
• Consent: Participants must be able to give written, informed consent as approved by the local IRB
• Newly Diagnosed Tumors: Participants with newly diagnosed Grade IV glioma who have had not been previously treated with cranial radiation therapy
• Recurrent Tumors: Participants with recurrent Grade IV gliomas who have failed cranial radiation therapy

You may not qualify if:

• Pregnant women or those who are breast feeding
• Individuals with history of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis
• Individuals with history of liver disease in last 12 months
• Individuals with AST, ALT, ALP, or bilirubin \>2.5x normal upper limit any time during the previous 2 months
• Individuals with plasma creatinine\>180 μmol/L
• Individuals who are unable to comply with photosensitivity precautions
• Individuals without a grade IV glioma

Sponsors & Collaborators

• Andrew Sloan, MD: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Andrew Sloan, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Neurosurgeons and investigators responsible for determining pathologic characteristics, for quantifying fluorescence images, for extracting chemical PpIX, for co-localizing fluorescence images with MR images will be blinded to the ALA dose and administration time. In case of emergency, such as toxicity or allergic reaction attributable to the drug, the research pharmacist on call will break the blind and inform the physician responsible for clinical management.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 12, 2008
• First Posted: September 15, 2008
• Study Start: December 8, 2009
• Primary Completion: September 15, 2018
• Study Completion: October 14, 2018
• Last Updated: September 17, 2021

Record last verified: 2021-09

Locations

US (1)