Anterior Temporal Lobectomy in Temporal Glioblastoma

NCT ID: NCT07021339

Last Updated: 2025-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

178 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-28

Study Completion Date

2031-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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Newly-diagnosed Glioblastoma Temporal Lobe

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gross total resection (GTR)

Complete resection of the contrast-enhancing tumor in Magnetic Resonance Imaging (MRI)

Group Type ACTIVE_COMPARATOR

Gross Total Resection (GTR)

Intervention Type PROCEDURE

Patients will be surgically treated with GTR in terms of removing 100% of the tumor tissue in gadolinium-enhanced MRI.

Anterior temporal lobectomy (ATL)

Anterior temporal lobectomy

Group Type EXPERIMENTAL

Anterior temporal lobectomy (ATL)

Intervention Type PROCEDURE

Patients 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.

Interventions

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Anterior temporal lobectomy (ATL)

Patients 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.

Intervention Type PROCEDURE

Gross Total Resection (GTR)

Patients will be surgically treated with GTR in terms of removing 100% of the tumor tissue in gadolinium-enhanced MRI.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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)
* In case further T1-contrast-enhancing and/or T2/FLAIR lesions are detected beyond the resection margins (6.5 cm on the non-dominant side and 4.0 cm on the dominant side), these lesions are not attributed to the tumor (except perifocal edema) but to other conditions according to the local treating neurosurgeon
* ≥ 18 and \< 75 years of age
* KPS ≥ 70%
* Estimated life expectancy of at least 6 months
* Written informed consent
* Cognitive state to understand the rationale and necessity of the study therapy and procedures
* Patient compliance and geographic proximity that allow adequate follow-up
* For patients with childbearing potential: negative serum pregnancy test (beta-HCG) at baseline visit, patient's commitment to use an approved contraceptive method during the trial and for 3 months after (Pearl index \< 1%)
* Adequate organ function at baseline visit that does not preclude alkylating chemotherapy and neurosurgical procedures (all criteria required):

* Adequate bone marrow reserve: white blood cell (WBC) count ≥ 3.000/µl; granulocyte count \> 1.500/µl; platelets ≥ 100.000/µl; haemoglobin ≥ 10 g/dl
* Adequate liver function: bilirubin \< 1.5 times above upper limit of normal range (ULN); alanine transaminase (ALT/SGPT) and aspartate transaminase (AST/ALAT) \< 3 times ULN
* Adequate renal function: creatinine \< 1.5 times ULN
* Adequate blood clotting: Partial Thromboplastin Time (PTT) not exceeding the upper limit of normal range and International Normalized Ratio (INR) \<1.5; in case of intake of anticoagulant medication or platelet function inhibitors, the coagulation analysis must show no detectable effect in specific blood tests (as described below) at the time of surgery, and discontinuation of the anticoagulant medication must be justifiable for at least 1 week postoperatively

* Direct acting oral anticoagulants (e.g., rivaroxaban, apixaban, edoxaban, dabigatran): anti-Factor Xa (aFXa)-activity within the normal range (rivaroxaban, apixaban, edoxaban), TT/TCT (thrombin clotting time) or ecarin clotting time (ECT) not exceeding the upper limit of normal range (Dabigatran) or verification of subtherapeutic drug levels (apixaban, edoxaban, rivaroxaban, dabigatran)
* Vitamin K antagonists (coumarins): INR \< 1.5
* Unfractionated heparin (UFH) and argatroban: activated Partial Thromboplastin Time (aPTT) not exceeding the upper limit of normal range
* Fractionated heparin/low-molecular-weight heparin (e.g., dalteparin, enoxaparin), heparinoid (e.g., fondaparinux, danaparoid): aFXa-activity within the normal range
* Antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor): platelet function analyzer (PFA) test not exceeding the upper limit of normal range (aspirin), whole blood aggregometry not below lower limits of normal range (clopidogrel, prasugrel, ticagrelor)

For details see study protocol.
Minimum Eligible Age

18 Years

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital RWTH Aachen, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

Kantonsspital Aarau, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Bonn, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

Dortmund Hospital, Neurosurgical Department

UNKNOWN

Sponsor Role collaborator

Helios Kliniken, Erfurt, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Essen, Department of Neurosurgery and Spine Surgery

UNKNOWN

Sponsor Role collaborator

University Hospital Frankfurt, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Giessen, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Medical Center Göttingen, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Medical Center Hamburg-Eppendorf, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

Heidelberg University Hospital, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

Jena University Hospital, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University of Cologne, Center of Neurosurgery Department of General Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Leipzig, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Medical Center Schleswig-Holstein/Lübeck, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

Medical Faculty University Hospital Magdeburg, University Clinic for Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Medical Center Mainz, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Mannheim, Medical Faculty Mannheim, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

Klinikum Rechts der Isar, Technical University of Munich, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

LMU University Hospital, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital of Münster, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Regensburg, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Medical Centre Rostock, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Tübingen, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital Ulm/Günzburg, University of Ulm, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

Medical University of Vienna, Department of Neurosurgery

UNKNOWN

Sponsor Role collaborator

University Hospital, Bonn

OTHER

Sponsor Role lead

Responsible Party

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Matthias Schneider

PD Dr. med.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University Hospital Bonn

Bonn, North Rhine-Westphalia, Germany

Site Status RECRUITING

Countries

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Germany

Facility Contacts

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Dr. Rafael Struck

Role: primary

+49 228 287 10586

Dr. med. Anna-Laura Potthoff

Role: backup

+49 228 287 16500

References

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Schneider M, Potthoff AL, Karpel-Massler G, Schuss P, Siegelin MD, Debatin KM, Duffau H, Vatter H, Herrlinger U, Westhoff MA. The Alcatraz-Strategy: a roadmap to break the connectivity barrier in malignant brain tumours. Mol Oncol. 2024 Dec;18(12):2890-2905. doi: 10.1002/1878-0261.13642. Epub 2024 Apr 3.

Reference Type BACKGROUND
PMID: 38567664 (View on PubMed)

Schneider M, Potthoff AL, Ahmadipour Y, Borger V, Clusmann H, Combs SE, Czabanka M, Duhrsen L, Etminan N, Freiman TM, Gerlach R, Gessler F, Giordano FA, Gkika E, Goldbrunner R, Guresir E, Hamou H, Hau P, Ille S, Jagersberg M, Keric N, Khaleghi-Ghadiri M, Konig R, Konczalla J, Krenzlin H, Krieg S, McLean AL, Layer JP, Lehmberg J, Malinova V, Meyer B, Meyer HS, Miller D, Muller O, Musahl C, Pregler BEF, Rashidi A, Ringel F, Roder C, Rossler K, Rohde V, Sandalcioglu IE, Schafer N, Schaub C, Schmidt NO, Schubert GA, Seidel C, Seliger C, Senft C, Shawarba J, Steinbach J, Stocklein V, Stummer W, Sure U, Tabatabai G, Tatagiba M, Thon N, Timmer M, Wach J, Wagner A, Wirtz CR, Zeiler K, Zeyen T, Schuss P, Surges R, Fuhrmann C, Paech D, Schmid M, Borck Y, Pietsch T, Struck R, Radbruch A, Helmstaedter C, Nemeth R, Herrlinger U, Vatter H. The ATLAS/NOA-29 study protocol: a phase III randomized controlled trial of anterior temporal lobectomy versus gross-total resection in newly-diagnosed temporal lobe glioblastoma. BMC Cancer. 2025 Feb 20;25(1):306. doi: 10.1186/s12885-025-13682-3.

Reference Type BACKGROUND
PMID: 39979825 (View on PubMed)

Borger V, Hamed M, Ilic I, Potthoff AL, Racz A, Schafer N, Guresir E, Surges R, Herrlinger U, Vatter H, Schneider M, Schuss P. Seizure outcome in temporal glioblastoma surgery: lobectomy as a supratotal resection regime outclasses conventional gross-total resection. J Neurooncol. 2021 Apr;152(2):339-346. doi: 10.1007/s11060-021-03705-x. Epub 2021 Feb 7.

Reference Type BACKGROUND
PMID: 33554293 (View on PubMed)

Schneider M, Potthoff AL, Keil VC, Guresir A, Weller J, Borger V, Hamed M, Waha A, Vatter H, Guresir E, Herrlinger U, Schuss P. Surgery for temporal glioblastoma: lobectomy outranks oncosurgical-based gross-total resection. J Neurooncol. 2019 Oct;145(1):143-150. doi: 10.1007/s11060-019-03281-1. Epub 2019 Sep 4.

Reference Type BACKGROUND
PMID: 31485921 (View on PubMed)

Karschnia P, Young JS, Dono A, Hani L, Sciortino T, Bruno F, Juenger ST, Teske N, Morshed RA, Haddad AF, Zhang Y, Stoecklein S, Weller M, Vogelbaum MA, Beck J, Tandon N, Hervey-Jumper S, Molinaro AM, Ruda R, Bello L, Schnell O, Esquenazi Y, Ruge MI, Grau SJ, Berger MS, Chang SM, van den Bent M, Tonn JC. Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group. Neuro Oncol. 2023 May 4;25(5):940-954. doi: 10.1093/neuonc/noac193.

Reference Type BACKGROUND
PMID: 35961053 (View on PubMed)

Roh TH, Kang SG, Moon JH, Sung KS, Park HH, Kim SH, Kim EH, Hong CK, Suh CO, Chang JH. Survival benefit of lobectomy over gross-total resection without lobectomy in cases of glioblastoma in the noneloquent area: a retrospective study. J Neurosurg. 2019 Mar 1;132(3):895-901. doi: 10.3171/2018.12.JNS182558. Print 2020 Mar 1.

Reference Type BACKGROUND
PMID: 30835701 (View on PubMed)

Schneider M, Ilic I, Potthoff AL, Hamed M, Schafer N, Velten M, Guresir E, Herrlinger U, Borger V, Vatter H, Schuss P. Safety metric profiling in surgery for temporal glioblastoma: lobectomy as a supra-total resection regime preserves perioperative standard quality rates. J Neurooncol. 2020 Sep;149(3):455-461. doi: 10.1007/s11060-020-03629-y. Epub 2020 Sep 29.

Reference Type BACKGROUND
PMID: 32990861 (View on PubMed)

Related Links

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Other Identifiers

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290/23

Identifier Type: OTHER

Identifier Source: secondary_id

70114652

Identifier Type: -

Identifier Source: org_study_id

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