5-ALA in Recurrent Glioma

Glioma Clinical Trial

Official title:

Barrow ALA Trial for Recurrent Gliomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02119338
• Other study ID #: 11BN092
• Status: Recruiting
• Phase: N/A
• First received: April 11, 2014
• Last updated: January 4, 2017
• Start date: February 2014
• Est. completion date: September 2017

Study information

• Verified date: January 2017
• Source: St. Joseph's Hospital and Medical Center, Phoenix
• Contact: Nader Sanai, MD
• Phone: 602-406-3770
• Email: Nader.Sanai[@]bnaneuro.net
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The investigators propose a single-center, non-randomized, single-arm study at the Barrow Neurological Institute/St. Joseph's Hospital for recurrent glioma. The 5-ALA for recurrent glioma study will correlate presence of fluorescence in tumor tissue with pathological findings. This will be done using three cohorts in dose escalation. The investigators' hypothesis is that (for both low- and high-grade gliomas,) a lower dose of 5-ALA will result in less false positive fluorescence.

Description:

The goal is to determine the dose of 5-ALA which promotes the lowest volume of residual disease after resection of recurrent high grade glioma without compromising the demarcation between recurrent high grade glioma and postoperative bed normal tissue.

Sub-goals:

1. To determine the impact of the dose of 5-ALA in improving volumetric extent of resection in patients with recurrent high grade gliomas

2. To determine the impact of the dose of 5-ALA in improving overall survival of recurrent high grade glioma patients

3. To determine the impact of the dose of 5-ALA in improving progression-free survival of recurrent high grade glioma patients

4. To determine the impact of the dose of 5-ALA on the neurological morbidity of recurrent high grade glioma patients.

Patients with presumed recurrent glioma will be entered into the trial. Those with recurrent disease will receive study drug (5-ALA) in one of three dose-escalated cohorts (5 mg/kg; 10 mg/kg; 20 mg/kg). Intraoperatively, patients will undergo resection with combined fluorescence microscopy and confocal microscopy. Resected tissue specimens corresponding to the presence of fluorescence will be sent to pathology for examination. Postoperatively, patients will have an MRI with and without contrast within 48 hours of surgery. Subsequent analysis of each patient will include assessment of the primary endpoint (volume of residual disease) by volumetrically quantifying the tumor before and after surgery using T1-weighted contrast-enhancement. Similarly, volumetric extent of resection will also be measured.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Presumed recurrent glioma

• Age > 18 years

• Normal bone marrow function (WBC > 3000, Platelets > 100,000)

Exclusion Criteria

• Pregnancy

• History of photosensitivity, porphyria, or exfoliative dermatitis

• Hepatic dysfunction in the last 12 months [defined by aspartate aminotransferase(AST), alanine aminotransferase (ALT) , alkaline phosphatase (ALP) , bilirubin > 2.5 x normal]

• Serum creatinine > 180 µmol/L

• Estimated Glomerular Filtration Rate (eGFR)< 60 ml/min/1.73m2

• Inability to undergo MRI with contrast

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• 5-ala
dose of 5-ala will be taken as either 5 mg/kg, 10 mg/kg, or 20 mg/kg approximately 3 hours before going to surgery.

Locations

Country	Name	City	State
United States	Barrow Neurological Institute at St. Joseph's Hospital and Medical Center	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
St. Joseph's Hospital and Medical Center, Phoenix

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of fluorescence in tumor tissue compared to tissue with treatment effect.	Correlation of fluorescence with pathological findings	day of surgery-1 day	No
Secondary	Extent of resection	A postoperative MRI with contrast will be acquired within 48 hours of surgery. Volumetric analysis of contract T1-weighted images (for low grade gliomas) will be compared to the preoperative sequences to calculate the volume of residual disease. Slice-by-slice assessment of pre- and postoperative tumor volume will be quantified by sequentially measuring the area of tumor on each slice and then integrating the combined measurements. This methodology has been previously reported (Sanai et al., Journal of Neurosurgery, 2010; Sanai et al, The New England Journal of Medicine, 2008)	time within 48 hours post operative	No
Secondary	Progression-free survival rate at 6 months		time from date of surgery to 6 months post surgery	No
Secondary	Overall survival		time from date of surgery to date of death from any cause, assessed up to 100 months	No