Anterior (front) temporal lobe removal for temporal glioblastoma

Randomized, Controlled Trial of Anterior Temporal Lobectomy Versus Gross Total Resection in Newly-diagnosed Temporal Glioblastoma (ATLAS/NOA-29)

This will see if removing the front part of the temporal lobe (anterior temporal lobectomy) helps people with newly diagnosed temporal-lobe glioblastoma live longer than standard complete tumor removal (gross-total resection).

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 178 (estimated)
• Ages: 18 Years to 74 Years
• Sex: All
• Sponsor: University Hospital, Bonn (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Bonn, North Rhine-Westphalia)
• Trial ID: NCT07021339 on ClinicalTrials.gov

What this trial studies

ATLAS/NOA-29 is a prospective, multicenter, randomized phase III trial comparing a standardized anterior temporal lobectomy (ATL) technique adapted from epilepsy surgery with conventional gross-total resection (GTR) for newly diagnosed glioblastoma confined to the anterior temporal lobe. Patients are randomized intraoperatively 1:1 after frozen-section confirmation of a diffuse high-grade glioma, and surgery follows predefined anatomical boundaries for supramarginal resection. The primary endpoint is overall survival, with a co-objective to confirm non-inferiority for health-related quality of life using validated instruments. Eligibility is limited to tumors within defined distances from the temporal pole (up to 6.5 cm non-dominant, 4.0 cm dominant) and where macroscopic complete resection is judged achievable by the neurosurgeon.

Who should consider this trial

Good fit: Ideal candidates are adults with newly diagnosed, contrast-enhancing glioblastoma localized to the anterior temporal lobe within the trial's distance limits (≤6.5 cm non-dominant side, ≤4.0 cm dominant side), confirmed as diffuse high-grade glioma on intraoperative frozen section, and judged by the surgeon to allow macroscopic complete resection.

Not a fit: Patients with tumors outside the defined anterior temporal boundaries, multifocal disease, lesions that preclude macroscopic complete resection, or pathology other than diffuse high-grade glioma are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, ATL could extend overall survival for patients with anterior temporal glioblastoma without compromising quality of life.

How similar studies have performed: Retrospective series and smaller prospective reports of supramarginal resections suggest possible survival gains but results are mixed, and this is among the first large randomized phase III efforts specifically testing an ATL approach for temporal glioblastoma.

Eligibility 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.

Where this trial is running

Bonn, North Rhine-Westphalia

• University Hospital Bonn — Bonn, North Rhine-Westphalia, Germany (RECRUITING)

Conditions: Newly-diagnosed Glioblastoma, Temporal Lobe, ATLAS/NOA-29, ATLAS, NOA-29, Anterior temporal lobectomy, gross total resection