MEDICO-ECONOMIC EVALUATION OF SURGERY GUIDED BY FLUORESCENCE FOR THE OPTIMIZATION OF RESECTION OF GLIOBLASTOMAS

Study Overview
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Brief Summary
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Glioblastoma is the most frequent primary malignant brain tumor in adults (3,000 new cases per year) and is characterized by a poor prognosis (median survival 12 months). Treatment is based mainly on surgical excision as complete as possible followed by an additional radiochemotherapy. The prognosis depends mainly on the quality of resection when it is macroscopically complete. Different techniques to support the surgical resection have been developed over the past 20 years. The reference technique is currently the intraoperative neuronavigation for guiding excision by matching the intraoperative tumor boundaries with those of the preoperative MRI. Its main drawback is the loss of precision during the resection related to changes in anatomical limits of the tumor. The per-operative fluorescence-guided surgery (FGS) is an innovative alternative technique to support the surgical resection. The 5-aminolevulinic acid (5-ALA), a molecule absorbed by the patient before surgery is captured specifically by the tumor cells and transformed into a fluorochrome revealed intraoperatively by a light source length adapted wave with a set of lenses included in the microscope. Resection is thus guided by this fluorescence whose disappearance translates complete tumor resection. Its interest is twofold: Increase the percentage of complete tumor resection. Improve disease-free survival and overall survival. The objective of the study is to compare the FGS to the intraoperative neuronavigation for the resection of glioblastoma, on a medical and economical level through a randomized, prospective, multicenter trial. The annual number of patients likely to benefit of this technique in France is estimated at 2200 new cases.

Detailed Description
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Main Outcome Measure: Percentage of patients with surgical resection of the tumor is complete, objectified by the absence of residual tumor on MRI early postoperative (within 48 hours) by a central committee of independent reading with qualitative analysis taking a contrast replay console for diagnostic use

Official Title
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Randomized, Prospective, Multicenter Blinding Singles With Arm A and Arm B Innovative Strategy Strategy Conventional

Conditions
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Glioblastoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years with no upper age limit Competent adult patient. Patient affiliated to the National Health Insurance. Patient with an intra-cerebral supra-tentorial hemispheric, newly diagnosed and previously untreated, which MRI characteristics are suggestive of a glioblastoma. Indication for surgical treatment by excision. Brain tumor location distant from critical functional areas allowing a wide resection of contrast enhancement on imaging, the a priori character completely resectable has been validated by an evaluation committee composed of three surgeons No-cons contain medical surgery, ASA score below 4. Patient eligible for further treatment by radiotherapy and concurrent chemotherapy followed by adjuvant chemotherapy according to the so called Stupp scheme (standard protocol of adjuvant chemoradiotherapy) Negative pregnancy test for women of childbearing age. Exclusion Criteria: Contraindications to performing an MRI (pacemaker). Glioblastoma known and previously treated with surgery, radiotherapy and / or chemotherapy. History of cancer. Anatomical Location of the tumor-cons indicating a wide excision, neurosurgeon at the discretion of medical officer participating center. Location tumor in the brain stem, the middle line, the basal ganglia and the posterior cranial fossa. Patient with cons-indication to the achievement of further treatment with radiotherapy and concurrent chemotherapy followed by adjuvant chemotherapy according to the scheme proposed by Stupp. (1) Patients with porphyria, renal insufficiency (creatinine> 177 μmolL), liver insufficency(gamma glutamyl transpeptidase> 100 U / L, prothrombin time <60%, bilirubin> 51μmol / L). Patient refused to sign an informed consent form. Ongoing participation of the patient to another clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-aminolévulinique acid (5-ALA)<br>5-aminolévulinique acid :microsurgical resection guided by fluorescence (CGF) in addition to the usual techniques of neuronavigation, after oral administration of 20mg/kg of 5-ALA 3-5 hours prior to surgical incision | Drug: 5-aminolévulinique acid (5-ALA)<br>* oral administration of 20mg/kg of 5-ALA 3-5 hours before the surgical incision<br>* Other names: Bras A;|
| Placebo Comparator: Placebo<br>Laroscorbine :microsurgical excision guided solely by neuronavigation, after oral administration of a placebo 3 to 5 hours before the surgical incision | Drug: Placebo<br>* Oral administration of 1g of ascorbic acid LAROSCORBINE in 50ml of water 3 hours before surgery<br>* Other names: Bras B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of complete tumor resection between the 2 arms | Evidenced of complete resection (absence of residual tumor on early postoperative MRI (within 48 hours)) will be assessed by a central independent committee with qualitative analysis of contrast enhancement replay on a console for diagnostic use. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of complete tumor resection between the 2 arms | Evidenced of complete resection (absence of residual tumor on early postoperative MRI (within 48 hours)) will be assessed by the neurosurgeon who conducted the surgery and the neuro-radiologist who conducted the RMI with qualitative analysis of contrast enhancement replay during the initial clinical analysis | less than 48 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, 5ALA, fluorescence, resection