The Use of 5-aminolevulinic Acid (ALA) as an Intraoperative Tumor Marker for Resection of Pediatric Central Nervous System (CNS) Tumors (5-ALA)

The Use of 5-aminolevulinic Acid (ALA) as an Intraoperative Tumor Marker for Resection of Pediatric CNS Tumors

Surgery is the cornerstone treatment of most pediatric CNS tumors, including astrocytomas, ependymomas, medulloblastomas, and many other pathologies.

In most pediatric CNS tumors, the aim of surgery is maximal tumor resection, while preserving neurological function. Extent of tumor residual has been shown to be a major prognostic factor for progression free survival (PFS), and survival in several malignant and low-grade tumors such as medulloblastomas, ependymomas, and astrocytic tumors.

5-aminolevulinic acid (5-ALA) has been shown to be valuable in intraoperative marking of various cancers. Following oral admission, during surgery, the tumor tissue is illuminated by blue light. Tumor cells tend to metabolize 5-ALA to a porphyrin named protoporhyrin IX (PpIX). PpIX reacts with the blue light and emits a pinky color (- fluorescence). This enables the surgeon to better identify tumor cells and perform a more extensive resection.

Over recent years, many studies have proven the efficacy using 5-ALA for resecting various intracranial and spinal tumors, thus achieving a better tumor control.

In the suggested study, we propose using the same technique for various pediatric central nervous system tumors.

We will focus on the correlation between various pathologies and the fluorescence, trying to deduce the role of 5-ALA in resection of specific pathologies.

Also, we will study the safety of 5-ALA use in the pediatric population.

Study Overview

• Status: Unknown
• Conditions: Central Nervous System Tumor, Pediatric
• Intervention / Treatment: Drug: 5ALA

Detailed Description

Following the above general description, eligible children will receive 5-aminolevulinic acid (5ALA) prior to surgery.

During surgery, careful attention will be payed to the fluorescence from the tumor, as well as the ability to differentiate between tumor and non tumorous tissue.

Comparisons between fluorescence and pathologies will be performed. Additionally, careful documentation of side effects will be done, to increase the safety of 5ALA use.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jonathan Roth, MD; Phone Number: 972-524262095; Email: jonaroth@gmail.com

Study Locations

• Israel
  • Tel-Aviv, Israel, 64239
    • Department of pediatric neurosurgery
    • Contact: Jonathan Roth, MD; Phone Number: 972-524262095; Email: jonaroth@gmail.com
    • Principal Investigator: Jonathan Roth, MD
    • Sub-Investigator: Shlomi Constantini, MD, MSc
    • Sub-Investigator: Liana Beni-Adani, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 3 -18 years old
• Any CNS related pathology (including intraaxial and extraaxial tumors, intracranial or spinal intradural) that is planned for either open (microscopic) resection (or biopsy), or lesions undergoing stereotactic biopsies.
• Parental consent
• No personal or familial (1st degree) history of porphyria
• Liver function test within normal limits (alanine aminotransferase (ALT), aspartate aminotransferase (AST)<2 * upper normal limit)
• Normal renal function (Cr <2)

Exclusion Criteria:

• Surgery with no microscopic use (i.e. purely endoscopic surgeries)
• History of hepatic disease within last 12 months
• History of cutaneous photosensitivity, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis, or porphyria
• Inability to comply with photosensitivity precautions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5ALA; All included patients will receive 20mg/kg of 5ALA (oral suspension) about 3 hours prior to surgery	Drug: 5ALA; 20mg/kg of oral suspension of 5ALA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sensitivity of 5ALA fluorescence to intraoperatively detect pediatric CNS tumor tissue	about 3hour following the 5ALA admission, the patient undergoes surgery. during surgery, global impression of tumor fluorescence will be appreciated (none, inhomogenous, intense homogenous) additionally, tumor samples will be taken from various regions, including various fluorescence regions, to try and correlate tumor regions (e.g. necrosis and viable tumor) with fluorescence (and measure the sensitivity of the 5ALA to the specific tumor)	up to 2 weeks
number of patients with 5ALA related side effects	5ALA is known to cause skin hypersensitivity reaction following direct sun light exposure, during the first 48 hours after admission. also, transient elevation in liver enzymes have been documented. the investigators will supervise these reactions during the postoperative phase	2 weeks

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2017

Study Registration Dates

• First Submitted: November 20, 2013
• First Submitted That Met QC Criteria: January 28, 2014
• First Posted (Estimate): January 30, 2014

Study Record Updates

• Last Update Posted (Estimate): January 30, 2014
• Last Update Submitted That Met QC Criteria: January 28, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: pediatrics; brain tumor; CNS; fluorescence; 5ALA
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: TASMC-13-JR-528-CTIL