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

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ClinicalTrials.gov Identifier: NCT00752323
Recruitment Status : Completed
First Posted : September 15, 2008
Last Update Posted : November 13, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE September 12, 2008
First Posted Date  ICMJE September 15, 2008
Last Update Posted Date November 13, 2019
Actual Study Start Date  ICMJE August 18, 2008
Actual Primary Completion Date September 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2011)
Assess 2 doses of 5-ALA [ Time Frame: 6 hours before midpoint of surgery ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2008)
Optimum dose and administration time of aminolevulinic acid for the detection of residual tumor by fluorescence imaging
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2011)
  • 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 [ Time Frame: Quantitative fluorescence imaging of tumor tissue and normal tissue at approximately the midpoint of surgery and then after maximal resection of the tumor. ]
    readings will be taken at the biopsied location with the PpIX point probe by the surgeon.
  • 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 [ Time Frame: Tumor tissue samples are obtained at the same two timepoints (the midpoint of surgery and then after maximal resection of the tumor) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2008)
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Imaging Procedure Using ALA in Finding Residual Tumor in Grade IV Malignant Astrocytoma
Official Title  ICMJE Fluorescence-Guided Detection of Malignant Gliomas: A Dose Ranging Study Using 5-Aminolevulinic Acid (ALA) Induced Protoporphyrin (PpIX) in a Multicenter Phase II Clinical Trial
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.

Detailed Description

OBJECTIVES:

Primary

  • Assess 2 doses of 5-ALA, 10kg/mg and 20kg/mg, to determine the optimum ALA dose in terms of both sensitivity and specificity for residual tumor. We will compare residual tumor detection by both in vivo qualitative and quantitative fluorescence imaging using histology of the biopsied tissue as the gold standard.

Secondary

  • Assess the correlation between the recorded in vivo qualitative assessment of fluorescence signal from the neurosurgeon with the post-surgical (i.e., ex vivo) absolute PpIX concentration detected both intraoperatively and in ex vivo tissue biopsies.

Tertiary

  • To determine the association between the presence of fluorescence in the surgical cavity and the post-operative image enhancement on MRI. This includes the relationship between the amount and location of residual tumor detected by fluorescence, PpIX concentration, and intra-operative frameless stereotaxy following maximal resection versus the amount and location of tumor imaged post-operatively via CT and/or MRI.

OUTLINE: This study will enroll evaluable participants undergoing surgical resection of malignant, grade IV gliomas in both of two groups: those with , newly diagnosed GBM and those with recurrent GBM. Participants in each group (primary vs recurrent GBM) will be randomized to one of 2 levels of ALA dose (10 and20 mg/kg) to be given orally at 6 hours prior to anticipated midpoint of surgery.

Participants who have consented to this protocol will be randomly assigned to one of two ALA dose groups. Randomization will be stratified by whether the tumor is newly diagnosed (i.e. de novo) or recurrent. The data center will prepare sealed, opaque envelopes with the randomized assignment to ALA dose and administration time and notify the pharmacy of the trial site so that so that the correct ALA dose can be prepared.

  • Arm I: Newly diagnosed GBM participants receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery.
  • Arm II: Newly diagnosed GBM participants receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
  • Arm III: Recurrent GBM participants receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery.
  • Arm IV: Recurrent GBM participants receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.

For both participants with new and recurrent disease, biopsies will be taken at up to six sites identified by the surgeon: in the tumor center, tumor edge, area surrounding the tumor (if safe), areas seen to fluoresce intraoperatively and an area with MR enhancement outside the tumor region (if this can be accomplished safely). Prior to collecting these biopsies readings will be taken at the biopsied location with the PpIX point probe by the surgeon. For each of the 6 biopsies, they will be divided into 3 parts and distributed for further analysis as follows: one portion will be sent to the pathologist for assessment of tumor percentage, one portion will be evaluated by the Division of Biophysics at the University of Toronto for PpIX concentration and the other for assessment of fluorescence.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Diagnostic
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE Drug: aminolevulinic acid
Given orally
Other Names:
  • δ-Aminolevulinic acid Hydrochloride
  • 5-Amino-4-oxopentanoic acid Hydrochloride
  • 5-Aminolaevulinic acid Hydrochloride
Study Arms  ICMJE
  • Experimental: Arm I: Newly diagnosed GBM 10mg/kg
    Arm I: Newly diagnosed GBM patients receive oral aminolevulinic acid(10mg/kg)at 6 hours before the midpoint of surgery.
    Intervention: Drug: aminolevulinic acid
  • Experimental: Arm II: Newly diagnosed GBM 20mg/kg
    Arm II: Newly diagnosed GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
    Intervention: Drug: aminolevulinic acid
  • Experimental: Arm III: Recurrent GBM 10mg/kg
    Arm III: Recurrent GBM patients receive oral aminolevulinic acid (10mg/kg)at 6 hours before the midpoint of surgery.
    Intervention: Drug: aminolevulinic acid
  • Experimental: Arm IV: Recurrent GBM 20mg/kg
    Arm IV: Recurrent GBM patients receive oral aminolevulinic acid (20mg/kg)at 6 hours before the midpoint of surgery.
    Intervention: Drug: aminolevulinic acid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 4, 2019)
73
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2008)
90
Actual Study Completion Date  ICMJE September 15, 2018
Actual Primary Completion Date September 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00752323
Other Study ID Numbers  ICMJE CASE1305
P30CA043703 ( U.S. NIH Grant/Contract )
CASE1305 ( Other Identifier: Case Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Andrew Sloan, MD University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP