Anterior Temporal Lobectomy in Temporal Glioblastoma
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-74
SponsorUniversity Hospital, Bonn
About this trial
The ATLAS/NOA-29 trial is a prospective, multicenter, phase III randomized controlled study evaluating whether anterior temporal lobectomy (ATL), a standardized resection technique adapted from epilepsy surgery, improves clinical outcomes in patients with newly diagnosed glioblastoma of the anterior temporal lobe compared to conventional gross-total resection (GTR). The rationale is based on the concept of glioblastoma as a diffusely connected tumor network, with infiltrative spread extending beyond MRI-detectable tumor margins. ATL offers a reproducible supramarginal resection approach within anatomical boundaries that are routinely respected in epilepsy surgery.
Patients are randomized intraoperatively in a 1:1 ratio following histopathological confirmation via intraoperative frozen section procedure. The trial's primary objective is to demonstrate superiority of ATL in overall survival (OS), while confirming non-inferiority in health-related quality of life (QoL), measured by the global health status scale of the European Organisation for Research and Treatment of Cancer (EORTC) - Quality of Life Questionnaire Core 30 (QLQ-C30). Secondary outcomes include progression-free survival (PFS), seizure control, neurocognitive functioning, and longitudinal assessments of selected EORTC QLQ-C30 and BN20 domains. A total of 178 patients will be enrolled over three years, with a minimum follow-up of three years. An interim safety analysis after inclusion of 57 patients will assess functional outcome differences using the modified Rankin Scale (mRS) at 6 months postoperatively. The study is powered (\>80%) to detect a survival benefit assuming a median OS increase from 17 to 27.5 months. If proven superior to GTR, ATL could emerge as the preferred surgical strategy for isolated temporal lobe glioblastoma, offering robust evidence in favor of extending supramarginal resection principles to the broader context of glioblastoma care.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Suspected glioblastoma with contrast-enhancement in preoperative MRI
Diffuse high-grade glioma in frozen section procedure, newly-diagnosed
Tumor localization (in gadolinium-enhanced MRI): solely temporal, non-dominant side (right hemisphere in right-handed patients, or left-handed patients after testing for dominance): within 6.5 cm from the temporal pole; dominant side (left hemisphere in right-handed patients, all left-handed patients unless additional testing for dominance performed): within 4.0 cm from the temporal pole, as determined dorsally along the Sylvian fissure.
Macroscopic complete resection (no remaining contrast-enhancing tumoral lesion on early postoperative MRI) is achievable (decision of the treating neurosurgeon)
Disqualifiers
None
Trial design
Design model
Parallel
Treatments tested in this trial
Anterior temporal lobectomy (ATL)
Procedure/SurgeryPatients assigned to the experimental group will undergo an anterior temporal lobectomy (ATL) according to established protocols adapted from epilepsy surgery. ATL is a reproducible and anatomically well-defined procedure routinely performed in patients with pharmacoresistant temporal lobe epilepsy. On the non-dominant hemisphere, the neocortical resection typically extends 6.5 cm posteriorly from the temporal pole, while on the dominant side, the resection length is limited to 4.0 cm, both measured along the superior temporal gyrus and guided by the Sylvian fissure. Language dominance is determined based on handedness, as specified in the inclusion criteria. In most cases, the lateral neocortical segment can be removed en bloc. The mesial component of ATL encompasses resection of the uncus, amygdala, and the anterior hippocampus, typically including both the head and body. Resection is carried out to the level of the tectal plate or, at minimum, to the lateral mesencephalic sulcus.
Gross Total Resection (GTR)
Procedure/SurgeryPatients will be surgically treated with GTR in terms of removing 100% of the tumor tissue in gadolinium-enhanced MRI.
Treatment groups
178 Participants
are divided into 2 treatment groupsGroup A: Gross total resection (GTR)Active comparator 1 intervention
Group B: Anterior temporal lobectomy (ATL)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Overall survival
OS in the modified intention to treat (mITT) population of patients with glioblastoma, Central Nervous System (CNS) World Health Organization (WHO) grade 4, Isocitrate Dehydrogenase wild-type (IDHwt)
Time frame
From randomization until death or 36 months after recruitment of the last patient2
Patient-reported Quality of Life
In case of significant OS differences, the patient-reported QoL domain "global health status" (EORTC QLQ-C30 questionnaire) in the modified intention to treat (mITT) population is the co-primary endpoint. Over-all superiority of ATL requires significantly prolonged OS and non-inferiority regarding the development of the global health status over time in the mITT population.
Time frame
From randomization until death or 36 months after recruitment of the last patientSecondary outcomes
1
Progression-free survival
Progression is defined as the first documented evidence of progression of disease according to the Response Assessment in Neuro-Oncology 2.0 (RANO 2.0) criteria. Progression will be evaluated using the RANO (Response Assessment in Neuro-Oncology) 2.0. criteria.
Time frame
PFS is measured from randomization at the day of surgery until progression or death. PFS will be assessed at the 12-week follow-up visit and at all subsequent visits scheduled at 12-week intervals up to three years.2
Neurocognitive Outcome
All patients will undergo testing with the Brain Lesion Tracking Test (BLTT). The test covers all relevant domains of neurocognition-including episodic and semantic memory as well as executive functions-without excluding patients due to neurological impairments such as visual deficits or hemiparesis. The BLTT includes interlocking word list learning with delayed free recall and recognition, semantic word generation and fluency, phonemic fluency, reverse digit span, and incidental memory, providing a rapid screening of neurocognitive function. Results are categorized into three performance domains: executive functions, episodic memory, and semantic memory. In addition, figural memory is assessed through a visual recognition task involving drawn objects presented on a series of cards.
Time frame
Cognitive performance across all domains will be quantitatively assessed at baseline (preoperatively), and at follow-up visits on day 90 (visit 8) and one year after surgery (visit 11).3
Karnofsky Performance Scale
Karnofsky Performance Scale (KPS) is an attempt to quantify cancer patients' general well-being and activities of daily life. The KPS ranking runs from 100 to 0, where 100 is "perfect" health and 0 is death.
Time frame
KPS will be assessed at baseline, on postoperative day 1, and at follow-up visits on days 3, 14, 30, and 90, and subsequently at 12-week intervals.4
Seizure outcome
Analysis of postoperative seizure outcome will be assessed referring to the ILAE classification system in the course of epilepsy surgical procedures: seizure freedom (ILAE class 1) will be de-fined as a favorable seizure outcome; ILAE classes 2-6 (i.e. pure auras, rare to no improvement and worsening of seizure frequency) will be referred to as unfavorable seizure outcome.
Time frame
Seizure outcome will be assessed at the 12 weeks, the 6 months and all 12 week follow-up examination.Sponsors and contacts
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University Hospital, Bonn
Lead sponsor
University Hospital, Aachen
Collaborator
Kantonsspital Aarau, Department of Neurosurgery
Collaborator
Dortmund Hospital, Neurosurgical Department
Collaborator
Helios Kliniken, Erfurt, Department of Neurosurgery
Collaborator
University Hospital, Essen
Collaborator
University Hospital Frankfurt, Department of Neurosurgery
Collaborator
University Hospital Giessen, Department of Neurosurgery
Collaborator
University Medical Center Göttingen, Department of Neurosurgery
Collaborator
Universitätsklinikum Hamburg-Eppendorf
Collaborator
University Hospital Heidelberg
Collaborator
Jena University Hospital
Collaborator
University of Cologne, Center of Neurosurgery Department of General Neurosurgery
Collaborator
University Hospital Leipzig, Department of Neurosurgery
Collaborator
University Medical Center Schleswig-Holstein/Lübeck, Department of Neurosurgery
Collaborator
Medical Faculty University Hospital Magdeburg, University Clinic for Neurosurgery
Collaborator
University Medical Center Mainz, Department of Neurosurgery
Collaborator
University Hospital Mannheim, Medical Faculty Mannheim, Department of Neurosurgery
Collaborator
Technical University of Munich
Collaborator
LMU University Hospital, Department of Neurosurgery
Collaborator
University Hospital of Münster, Department of Neurosurgery
Collaborator
University Hospital Regensburg
Collaborator
University Medical Center Rostock
Collaborator
University Hospital Tübingen, Department of Neurosurgery
Collaborator
University Hospital Ulm/Günzburg, University of Ulm, Department of Neurosurgery
Collaborator
Medical University of Vienna, Department of Neurosurgery
Collaborator
Source ClinicalTrials.gov