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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Case Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00752323
First received: September 12, 2008
Last updated: May 1, 2014
Last verified: May 2014
  Purpose

RATIONALE: Imaging procedures that use aminolevulinic acid may help find and diagnose residual tumor in patients 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 patient survival.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: aminolevulinic acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Assess 2 doses of 5-ALA [ Time Frame: 6 hours before midpoint of surgery ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: August 2008
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: aminolevulinic acid
Given orally
Other Names:
  • δ-Aminolevulinic acid Hydrochloride
  • 5-Amino-4-oxopentanoic acid Hydrochloride
  • 5-Aminolaevulinic acid Hydrochloride
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.
Drug: aminolevulinic acid
Given orally
Other Names:
  • δ-Aminolevulinic acid Hydrochloride
  • 5-Amino-4-oxopentanoic acid Hydrochloride
  • 5-Aminolaevulinic acid Hydrochloride
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.
Drug: aminolevulinic acid
Given orally
Other Names:
  • δ-Aminolevulinic acid Hydrochloride
  • 5-Amino-4-oxopentanoic acid Hydrochloride
  • 5-Aminolaevulinic acid Hydrochloride
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.
Drug: aminolevulinic acid
Given orally
Other Names:
  • δ-Aminolevulinic acid Hydrochloride
  • 5-Amino-4-oxopentanoic acid Hydrochloride
  • 5-Aminolaevulinic acid Hydrochloride

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 patients undergoing surgical resection of malignant, grade IV gliomas in both of two groups: those with , newly diagnosed GBM and those with recurrent GBM. Patient, 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.

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

For both patients 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.

  Eligibility

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

Inclusion Criteria:

  • 18 years or older
  • 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: Patients must be able to give written, informed consent as approved by the local IRB
  • Newly Diagnosed Tumors: Patients with newly diagnosed Grade IV glioma who have had not been previously treated with cranial radiation therapy
  • Recurrent Tumors: Patients 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
  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: NCT00752323

Contacts
Contact: Andrew Sloan, MD 216-844-6054 andrew.sloan@uhhospitals.org

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Andrew Sloan, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00752323     History of Changes
Other Study ID Numbers: CASE1305, P30CA043703, CASE1305
Study First Received: September 12, 2008
Last Updated: May 1, 2014
Health Authority: United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Aminolevulinic Acid
Dermatologic Agents
Pharmacologic Actions
Photosensitizing Agents
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014