Randomized, Controlled Trial of Anterior Temporal Lobectomy Versus Gross Total Resection in Newly-diagnosed Temporal Glioblastoma (ATLAS/NOA-29)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
研究组 & 干预措施
Gross total resection (GTR)
Complete resection of the contrast-enhancing tumor in Magnetic Resonance Imaging (MRI)
干预措施: Gross Total Resection (GTR) (Procedure)
Anterior temporal lobectomy (ATL)
Anterior temporal lobectomy
干预措施: Anterior temporal lobectomy (ATL) (Procedure)
结局指标
主要结局
Overall survival
时间窗: From randomization until death or 36 months after recruitment of the last patient
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)
Patient-reported Quality of Life
时间窗: From randomization until death or 36 months after recruitment of the last patient
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.
次要结局
- 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.)
- Quality-of-life (QoL)(QoL will be assessed at baseline, at follow-up visits on days 14, 30, and 90, and subsequently at 24-week intervals.)
研究者
Matthias Schneider
PD Dr. med.
University Hospital, Bonn