Fluorescence-guided Resection of Malignant Gliomas With 5-Aminolevulinic Acid

Fluorescence-guided Resection of Malignant Gliomas With 5-Aminolevulinic Acid (5-ALA) vs. Conventional Resection

The aim of the study "Fluorescence-guided resection of malignant gliomas with 5-Aminolevulinic acid (5-ALA) vs. conventional resection" is to determine how accurately contrast agent-accumulating tumour can be removed by primary surgery and to assess the clinical usefulness of this method.

Study Overview

• Status: Completed
• Conditions: Brain Cancer; Brain Tumors; Brain Tumor, Primary; Primary Brain Tumors; Cancer of Brain
• Intervention / Treatment: Drug: 5-aminolevulinic acid (5-ALA)

Detailed Description

Malignant gliomas are locally invasive tumors that carry a dismal prognosis despite a combination of surgery, radiotherapy and chemotherapy. Cytoreductive surgery is generally considered beneficial but complete resection of contrast enhancing tumor is achieved in less than 20 % of patients, one reason being the difficulty in discerning marginal, enhancing tumor intraoperatively.

Five-aminolevulinic acid (5-ALA) leads to the accumulation of fluorescent porphyrins in malignant gliomas, a phenomenon under exploration for intraoperative identification and resection of these tumors. This study investigated the benefit derived from fluorescent-guided resections using 5-ALA on surgical radicality, progression-free survival and morbidity.

• Study Type: Interventional
• Enrollment (Actual): 415
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 72 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Radiological suspicion of a unilocular malignant glioma with distinct ring- or garland-shaped contrast agent-accumulating tumour structures and a core of reduced intensity in the MRI (central necroses) with no significant non-staining tumour tissue (exclusion of a secondary malignant glioma).
• Indication for surgical tumour resection. If radical resection is planned, the location of the contrast agent-accumulating tumour should allow complete resection.
• First operation of the tumour, no other tumour-specific pretreatment
• Karnofsky at least 70 %
• Patient's written informed consent
• Age 18-72 years

Exclusion Criteria:

• Tumour location in the midline, basal ganglia, cerebellum or brain stem
• More than one contrast agent-accumulating lesion unrelated to the primary tumour or extracerebral metastases
• Porphyria, hypersensitivity to porphyrins
• Renal insufficiency: Creatinine > 2.0 mg/dl
• Hepatic insufficiency: Bilirubin > 3 mg/dl
• Quick test < 60 %
• gamma-GT > 70 U/I
• Malignancies other than basaliomas
• Existing or planned pregnancy or lactation, or inadequate contraception
• Simultaneous participation in another clinical trial or participation in another clinical trial in the 30 days preceding randomisation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 5-aminolevulinic acid	Drug: 5-aminolevulinic acid (5-ALA); 1.5 grams 5-ALA dissolved in 50 ml water, single dose, orally, 2-4 hours prior to surgery
NO_INTERVENTION: Conventional resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1. Percentage of patients with a histologically confirmed malignant glioma (grade III or IV -WHO) without definite residual contrast agent-accumulating tumour in the early post-operative control MRI (within 72 hours of the operation).	Within 72 hours after surgery
2. Progression-free survival 6 months after primary surgical treatment of a malignant gli-oma in patients with histologically confirmed malignant glioma (grade III or IV -WHO).	Within 6 month after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
1. Overall survival.	Until 18 months after surgery
2. Progression-free survival (PFS) 9, 12, 15 and 18 months after primary surgical treatment	Until 18 months after surgery
3. Volume of residual tumour	After surgery
4. Toxicity after oral administration of 5-Aminolevulinic acid.	Until 18 month after surgery
5. Neurological condition 7 days, 6 and 12 weeks, 6, 9, 12, and 18 months after primary surgical treatment	Until 18 month after surgery

Collaborators and Investigators

• Sponsor: medac GmbH
• Investigators: Study Chair: Hans-Juergen Reulen, MD, Ludwig-Maximilians - University of Munich

Publications and helpful links

General Publications

• Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. doi: 10.1016/S1470-2045(06)70665-9.

Study record dates

Study Major Dates

• Study Start: October 1, 1999
• Primary Completion (ACTUAL): July 1, 2004

Study Registration Dates

• First Submitted: October 18, 2005
• First Submitted That Met QC Criteria: October 18, 2005
• First Posted (ESTIMATE): October 19, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): April 26, 2012
• Last Update Submitted That Met QC Criteria: April 25, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Glioma; Brain Neoplasms; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: MC-ALS.3/GLI