Clinical trial NCT02632370: 5-Aminolevulinic Acid (5-ALA) to Enhance Visualization of Malignant Tumor
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 type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Malignant Gliomas
Keywords: Malignant Gliomas
5-ALA
tumor resection
malignant tumor
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
First posted: 2015-12-16
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with new or recurrent malignant gliomas

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.

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of diagnostic tissue presence
timeFrame: 6 weeks
Secondary outcomes:
measure: Presence of malignant glioma tumor cells
timeFrame: 6 weeks
measure: WHO tumor type with grading
timeFrame: 6 weeks
measure: Ki-67 proliferation index
timeFrame: 6 weeks
measure: Karnofsky Performance Scale
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Regional Medical Center
state: Idaho
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Cloud
country: United States
facility: CentraCare St. Cloud Hospital
state: Minnesota
city: Kansas City
country: United States
facility: St. Luke's Marion Bloch Neuroscience Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico School of Medicine, Department of Neurosurgery
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State- Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Massachusetts General Hospital
name: Bob Carter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: