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

Malignant Gliomas Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02632370
• Other study ID #: GCO 15-2034-0001
• Secondary ID: CGH932015PRMC 15
• Status: Completed
• Start date: May 2016
• Est. completion date: December 31, 2018

Study information

• Verified date: February 2019
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: December 31, 2018
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glioma
• Malignant Gliomas
• Neoplasms

Intervention

Drug:
• Gliolan®
single dose of oral 5-ALA (20mg/kg bodyweight) at 3 hours (range 2-5 hours) given preoperatively

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

Locations

Country	Name	City	State
United States	University of New Mexico School of Medicine, Department of Neurosurgery	Albuquerque	New Mexico
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Delray Medical Center	Delray Beach	Florida
United States	Henry Ford Hospital	Detroit	Michigan
United States	Penn State- Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	St. Luke's Marion Bloch Neuroscience Institute	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	CentraCare St. Cloud Hospital	Saint Cloud	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	George Washington University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Constantinos Hadjipanayis	Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of diagnostic tissue presence	Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.	6 weeks
Secondary	Presence of malignant glioma tumor cells	Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.	6 weeks
Secondary	WHO tumor type with grading	Pathologic confirmation of tumor type will be made by a pathologist who will not be informed of the fluorescence status of the tissue samples.	6 weeks
Secondary	Ki-67 proliferation index	Ki-67 is a prognostic marker for cancer	6 weeks
Secondary	Karnofsky Performance Scale	Scale from 0-100, function from low to high, with 100 being normal	6 weeks