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5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Malignant Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02632370
Recruitment Status : Completed
First Posted : December 16, 2015
Last Update Posted : February 25, 2019
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Constantinos Hadjipanayis, Icahn School of Medicine at Mount Sinai

Brief Summary:
In support of the US marketing application for 5-ALA, this single arm trial is being conducted to establish the efficacy and safety of Gliolan® (5-ALA) in patients with newly diagnosed or recurrent malignant gliomas. The hypothesis of the study is Gliolan® (5-ALA), as an adjunct to tumor resection, is safe and that real-time tissue fluorescence correlates with malignant histopathology. The primary objective in this single arm study is to define the positive predictive value (PPV) of Gliolan®-induced PPIX fluorescence for malignant tumor at the time of initial resection and first use of FGS by taking a biopsy of tissue presenting with red fluorescence when observed during the course of resection of new or recurrent malignant gliomas. The functionality and performance reliability of the blue light excitation microscope platforms will be assessed.

Condition or disease Intervention/treatment
Malignant Gliomas Drug: Gliolan® Procedure: Fluorescence-Guided Surgery

Detailed Description:

Primary Objectives

  • To determine whether Gliolan® (5-ALA)-induced PPIX fluorescence correlates with malignant tumor histopathology (in a minimum of 3-5 serial biopsies taken from the red fluorescent region of tissue resection).
  • To determine the patient safety profile of both oral Gliolan® (5-ALA), as well as use of the fluorescence operative microscope. These will include use of commonly accepted toxicity measures as well as recording surgically-related neurological deficits within the six weeks after surgery.
  • To determine functionality and performance reliability of the blue light excitation microscope platforms (Zeiss Pentero, Leica OH4, Leica OH6 and others).

Secondary Objectives

  • To correlate PPIX-containing extracellular microvesicles recovered from blood (at multiple time points prior to and following tumor resection) with the pre-operative MRI tumor volume.
  • To characterize the presence and longitudinal changes in microvesicle biomarkers recovered from blood evaluating EGFRvIII, IDH1/2 wt and mutations and others. These microvesicular blood genes will be identified and correlated with the same microvesicular genes identified in tissue at the time of surgery.

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Study Type : Observational
Actual Enrollment : 69 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multicenter Study of 5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Malignant Tumor in Patients With Newly Diagnosed or Recurrent Malignant Gliomas: A Safety, Histopathology, and Correlative Biomarker Study
Study Start Date : May 2016
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018


Group/Cohort Intervention/treatment
Gliolan®
Gliolan® is presented as a powder for oral solution in 60 ml colorless glass vials. The formulation contains 1.5 g 5-aminolevulinic acid hydrochloride corresponding to 1.17 g of 5-aminolevulinic acid. The oral solution is intended for single (partial) use.
Drug: Gliolan®
single dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively
Other Name: 5-ALA

Procedure: Fluorescence-Guided Surgery
performed utilizing blue light. At least 3-5 fluorescent tissue samples will be taken.
Other Name: FGS




Primary Outcome Measures :
  1. Incidence of diagnostic tissue presence [ Time Frame: 6 weeks ]
    Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.


Secondary Outcome Measures :
  1. Presence of malignant glioma tumor cells [ Time Frame: 6 weeks ]
    Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.

  2. WHO tumor type with grading [ Time Frame: 6 weeks ]
    Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.

  3. Ki-67 proliferation index [ Time Frame: 6 weeks ]
    Ki-67 is a prognostic marker for cancer

  4. Karnofsky Performance Scale [ Time Frame: 6 weeks ]
    Scale from 0-100, function from low to high, with 100 being normal


Biospecimen Retention:   Samples With DNA
whole blood, tumor samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with new or recurrent malignant gliomas
Criteria

Inclusion Criteria:

  • Subjects included must have an MRI documenting a primary brain tumor for which resection is indicated and has been planned. These patients will include those with newly diagnosed or recurrent malignant gliomas. Standard criteria for diagnosis will include a distinct ring-like pattern of contrast enhancement with thick irregular walls on MRI for patients with a presumed newly diagnosed malignant glioma.
  • Age 18-80.
  • Karnofsky>60%.
  • 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 AST (SGOT)/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 5-aminolevulinic Acid (5-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. A pregnancy test will be performed for all women of childbearing ability prior to surgery (see Exclusion Criteria below). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document. Translation will be provided as appropriate by institution.
  • Inclusion of Women and Minorities: Both men and women and members of all ethnic groups are eligible for this trial.

Exclusion Criteria:

  • Patients with radiographic tumors of, or involving, nonresectable midline, the basal ganglia, or brain stem as assessed by MRI.
  • 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 h.
  • Personal or family history of porphyria.
  • 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. . Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 5-aminolevulinic acid (5-ALA), breastfeeding should be discontinued if the mother is treated with 5-aminolevulinic acid (5-ALA).
  • Women who are pregnant will be excluded from the trial as aminolevulinic acid (ALA) is unknown to be teratogenic or have abortifacient effects Prior history of GI perforation, diverticulitis, and/or peptic ulcer disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02632370


Locations
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United States, District of Columbia
George Washington University
Washington, District of Columbia, United States, 20037
United States, Florida
Delray Medical Center
Delray Beach, Florida, United States, 33484
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Idaho
Saint Alphonsus Regional Medical Center
Boise, Idaho, United States, 83706
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Minnesota
CentraCare St. Cloud Hospital
Saint Cloud, Minnesota, United States, 56303
United States, Missouri
St. Luke's Marion Bloch Neuroscience Institute
Kansas City, Missouri, United States, 64111
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Mexico
University of New Mexico School of Medicine, Department of Neurosurgery
Albuquerque, New Mexico, United States, 87131
United States, New York
Mount Sinai Beth Israel
New York, New York, United States, 10003
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
United States, Pennsylvania
St. Luke's University Health Network
Bethlehem, Pennsylvania, United States, 18015
Penn State- Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Constantinos Hadjipanayis
Massachusetts General Hospital
Investigators
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Principal Investigator: Bob Carter, MD, PhD Massachusetts General Hospital

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Responsible Party: Constantinos Hadjipanayis, Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT02632370     History of Changes
Other Study ID Numbers: GCO 15-2034-0001
CGH932015 ( Other Identifier: Clinical Trials Regulatory Compliance Specialists )
PRMC 15-085 ( Other Identifier: Mount Sinai Hospital )
First Posted: December 16, 2015    Key Record Dates
Last Update Posted: February 25, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Constantinos Hadjipanayis, Icahn School of Medicine at Mount Sinai:
Malignant Gliomas
5-ALA
tumor resection
malignant tumor

Additional relevant MeSH terms:
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Glioma
Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aminolevulinic Acid
Photosensitizing Agents
Dermatologic Agents