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

Phase 3

Completed

• Conditions: Brain Cancer; Brain Tumors; Cancer of Brain; Primary Brain Tumors; Brain Tumor, Primary
• Interventions: Drug: 5-aminolevulinic acid (5-ALA)

• Registration Number: NCT00241670
• Lead Sponsor: medac GmbH

Brief Summary

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.

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 Timeline

• Study Start: 1999-10
• Primary Completion: 2004-07
• Study First Submitted: 2005-10-18
• Study First Submitted QC: 2005-10-18
• Study First Posted: 2005-10-19
• Status Verified: 2012-04
• Last Update Submitted: 2012-04-25
• Last Update Posted: 2012-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 415

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
5-aminolevulinic acid	5-aminolevulinic acid (5-ALA)	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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