Clinical trial NCT00241670: Fluorescence-guided Resection of Malignant Gliomas With 5-Aminolevulinic Acid
Official title: Fluorescence-guided Resection of Malignant Gliomas With 5-Aminolevulinic Acid (5-ALA) vs. Conventional Resection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Cancer
Brain Tumors
Cancer of Brain
Primary Brain Tumors
Brain Tumor, Primary
Lead sponsor: medac GmbH
Sponsor class: INDUSTRY
First posted: 2005-10-19
Enrollment: 415
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Within 72 hours after surgery
measure: 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).
timeFrame: Within 6 month after surgery
Secondary outcomes:
measure: 1. Overall survival.
timeFrame: Until 18 months after surgery
measure: 2. Progression-free survival (PFS) 9, 12, 15 and 18 months after primary surgical treatment
timeFrame: Until 18 months after surgery
measure: 3. Volume of residual tumour
timeFrame: After surgery
measure: 4. Toxicity after oral administration of 5-Aminolevulinic acid.
timeFrame: Until 18 month after surgery
measure: 5. Neurological condition 7 days, 6 and 12 weeks, 6, 9, 12, and 18 months after primary surgical treatment
timeFrame: Until 18 month after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Ludwig-Maximilians - University of Munich
name: Hans-Juergen Reulen, MD
role: STUDY_CHAIR
References:
citation: 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.