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

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ClinicalTrials.gov Identifier: NCT01811121
Recruitment Status : Unknown
Verified October 2016 by Hospices Civils de Lyon.
Recruitment status was:  Active, not recruiting
First Posted : March 14, 2013
Last Update Posted : October 5, 2016
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE February 21, 2013
First Posted Date  ICMJE March 14, 2013
Last Update Posted Date October 5, 2016
Study Start Date  ICMJE February 2013
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2013)
Comparison of complete tumor resection between the 2 arms [ Time Frame: 48 hours ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2013)
Comparison of complete tumor resection between the 2 arms [ Time Frame: less than 48 hours after surgery ]
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 12, 2013)
  • Diagnostic value of the two intraoperative techniques [ Time Frame: 60 months ]
    Evaluate the sensitivity, specificity, positive predictive value and negative by correlating the results of pathological analysis of resection edge with intraoperative findings of the surgeon at the end of resection.
  • Quantification of residual tumor (contrast enhancement) on MRI post-opératre early (before 48 hours) [ Time Frame: before 48 hours ]
    It will be performed by three study investigators (Dr. Pallud, Department of Neurosurgery, Centre Hospitalier Sainte-Anne, Paris; Dr. Guyotat, D department of Neurosurgery, Hospices Civils de Lyon, Lyon, Dr. Metellus, neurosurgery department, Assistance Publique - Hôpitaux de Marseille) and read separately. The volume analysis will be done by segmentation using the OsiriX software on postoperative MRI and MRI pre-operative
  • Progression Free survival rate at 6 months [ Time Frame: 6 months ]
    Progression is defined by the appearance of a new tumor lesion which minimum volume will be set to 0.175 cm3, by the increase of the residual tumor volume of 25% or more, or by the need to increase corticosteroid therapy. The period of progression free survival is defined as the time from the date of tumor resection and date of diagnosis of tumor progression or the date last news or date of endpoint. Progression Free survival rate at 6 months will be analyzed according to surgical approach used, according to the completeness or incompleteness of resection and by centers
  • Overall survival at 24 months [ Time Frame: 24 months ]
    It will be estimated from the number of patients who died of whatever cause. The overall survival time is defined as the time between the date of tumor resection and date of death from any cause or date of last news or the date of endpoint. The overall survival at 24 months will be analyzed according to surgical approach used, according to the completeness or incompleteness of resection and by centers.
  • Overall survival at 60 months [ Time Frame: 60 months ]
    It will be estimated from the number of patients who died of whatever cause. The overall survival time is defined as the time between the date of tumor resection and date of death from any cause or date of last news or the date of endpoint. The overall survival at 60 months will be analyzed according to surgical approach used, according to the completeness or incompleteness of resection and by centers.
  • Quality of life [ Time Frame: every 3 months ]
    Evaluation of quality of life every 3 months using the EORTC questionnaire QLQ-C30 with the specific brain tumors module BN20.
  • Evaluation of early and late morbidity [ Time Frame: in 8 days and late morbidity at 3 months ]
    Evaluation of early morbidity in 8 days and late morbidity at 3 months (neurological deficit, surgical site infection, secondary epilepsy, Karnofsky score, performance status WHO).
  • Comparison of surgical procedure duration between the 2 arms [ Time Frame: 60 months ]
  • Medico-economic evaluation of the 2 procedure [ Time Frame: 60 months ]
    Comparison of the differential cost effectiveness ratio between the 2 strategies
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE MEDICO-ECONOMIC EVALUATION OF SURGERY GUIDED BY FLUORESCENCE FOR THE OPTIMIZATION OF RESECTION OF GLIOBLASTOMAS
Official Title  ICMJE Randomized, Prospective, Multicenter Blinding Singles With Arm A and Arm B Innovative Strategy Strategy Conventional
Brief Summary

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 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Drug: 5-aminolévulinique acid (5-ALA)
    oral administration of 20mg/kg of 5-ALA 3-5 hours before the surgical incision
    Other Name: Bras A
  • Drug: Placebo
    Oral administration of 1g of ascorbic acid LAROSCORBINE in 50ml of water 3 hours before surgery
    Other Name: Bras B
Study Arms  ICMJE
  • Experimental: 5-aminolévulinique acid (5-ALA)
    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
    Intervention: Drug: 5-aminolévulinique acid (5-ALA)
  • Placebo Comparator: Placebo
    Laroscorbine :microsurgical excision guided solely by neuronavigation, after oral administration of a placebo 3 to 5 hours before the surgical incision
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: October 4, 2016)
170
Original Estimated Enrollment  ICMJE
 (submitted: March 12, 2013)
204
Estimated Study Completion Date  ICMJE August 2019
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01811121
Other Study ID Numbers  ICMJE 2011-697
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jacques GUYOTAT, MD Hospices Civils de Lyon
PRS Account Hospices Civils de Lyon
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP