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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Brain Cancer, Brain Tumors, Cancer of Brain, Primary Brain Tumors, Brain Tumor, Primary

Intervention / Treatment
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* Drug: 5-aminolevulinic acid (5-ALA)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-aminolevulinic acid<br> | Drug: 5-aminolevulinic acid (5-ALA)<br>* 1.5 grams 5-ALA dissolved in 50 ml water, single dose, orally, 2-4 hours prior to surgery<br>|
| No Intervention: Conventional resection<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |