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

• ClinicalTrials.gov Identifier: NCT02632370
• Recruitment Status: Completed
• First Posted: December 16, 2015
• Last Update Posted: February 25, 2019
• Sponsor: Constantinos Hadjipanayis
• Collaborator: Massachusetts General Hospital
• Information provided by (Responsible Party): Constantinos Hadjipanayis, Icahn School of Medicine at Mount Sinai

Study Description

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.

Study Design

• 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

Groups and Cohorts

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

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

Locations

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

• Principal Investigator: Bob Carter, MD, PhD; Massachusetts General Hospital

More Information

• 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
• Last Update Posted: February 25, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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:

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