Anterior Temporal Lobectomy in Temporal Glioblastoma

NCT07021339 | Recruiting Phase 3 DMC

• 2 other identifiers: 70114652290/23
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Newly-diagnosed Glioblastoma; Temporal Lobe

Keywords

ATLAS/NOA-29; ATLAS; NOA-29; Anterior temporal lobectomy; gross total resection

Outcome Measures

Primary Outcomes (2)

• 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)

  From randomization until death or 36 months after recruitment of the last patient

• 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.

  From randomization until death or 36 months after recruitment of the last patient

Secondary Outcomes (6)

• Progression-free survival

  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.

• Neurocognitive Outcome

  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).

• Karnofsky Performance Scale

  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.

• Seizure outcome

  Seizure outcome will be assessed at the 12 weeks, the 6 months and all 12 week follow-up examination.

• Modified Rankin Scale assessment (mRS)

  The mRS 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.

Study Arms (2)

Gross total resection (GTR)

ACTIVE COMPARATOR

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

Procedure: Gross Total Resection (GTR)

Anterior temporal lobectomy (ATL)

EXPERIMENTAL

Anterior temporal lobectomy

Procedure: Anterior temporal lobectomy (ATL)

Interventions

Anterior temporal lobectomy (ATL) 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.

Anterior temporal lobectomy (ATL)

Gross Total Resection (GTR) PROCEDURE

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

Gross total resection (GTR)

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

* 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University Hospital, Bonn: lead
• University Hospital RWTH Aachen, Department of Neurosurgery: collaborator
• Kantonsspital Aarau, Department of Neurosurgery: collaborator
• University Hospital Bonn, Department of Neurosurgery: collaborator
• Dortmund Hospital, Neurosurgical Department: collaborator
• Helios Kliniken, Erfurt, Department of Neurosurgery: collaborator
• University Hospital Essen, Department of Neurosurgery and Spine Surgery: collaborator
• University Hospital Frankfurt, Department of Neurosurgery: collaborator
• University Hospital Giessen, Department of Neurosurgery: collaborator
• University Medical Center Göttingen, Department of Neurosurgery: collaborator
• University Medical Center Hamburg-Eppendorf, Department of Neurosurgery: collaborator
• Heidelberg University Hospital, Department of Neurosurgery: collaborator
• Jena University Hospital, Department of Neurosurgery: 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
• Klinikum Rechts der Isar, Technical University of Munich, Department of Neurosurgery: collaborator
• LMU University Hospital, Department of Neurosurgery: collaborator
• University Hospital of Münster, Department of Neurosurgery: collaborator
• University Hospital Regensburg, Department of Neurosurgery: collaborator
• University Medical Centre Rostock, Department of Neurosurgery: 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

Study Sites (1)

University Hospital Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

RECRUITING

Related Publications (7)

• 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.

  PMID: 38567664 BACKGROUND

• 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.

  PMID: 39979825 BACKGROUND

• 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.

  PMID: 33554293 BACKGROUND

• 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.

  PMID: 31485921 BACKGROUND

• 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.

  PMID: 35961053 BACKGROUND

• 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.

  PMID: 30835701 BACKGROUND

• 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.

  PMID: 32990861 BACKGROUND

Related Links

• ATLAS/NOA-29 Website

MeSH Terms

Interventions

Anterior Temporal Lobectomy

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Neurosurgical Procedures

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med.

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: June 13, 2025
• Study Start: November 28, 2024
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2031
• Last Updated: June 13, 2025

Record last verified: 2025-06

Locations

DE (1)