Sub-lobectomy for IDH Wild-type and TERT Promoter Mutant Glioblastoma

NCT06368934 | Not Yet Recruiting

• 1 other identifier: KY2024-011
• Study Type: interventional
• Target: 326
• Locations: 1 country
• Sites: 1

Brief Summary

Glioblastoma is recognized as the most common and aggressive form of primary malignant brain tumor, with treatment options that are limited and prognosis that is extremely poor, showing median progression-free survival of 12 months and median overall survival of less than 18 months. Surgical resection plays a critical role in the treatment, with the extent of resection significantly impacting patient outcomes. Historical approaches to surgical resection have evolved, moving from radical strategies to more conservative ones that aim to preserve normal brain function while removing the tumor as completely as possible. Recent studies have suggested that increasing the extent of surgical resection, particularly along the T2 FLAIR border rather than the traditional T1-enhanced border, can significantly improve patient prognosis. There is, however, a lack of consensus on the optimal surgical approach, and the heterogeneity of tumors presents challenges in standardizing surgical strategies. Extended resection has been shown to prolong survival, and novel intraoperative molecular diagnostics have emerged to improve accuracy in tumor classification and prognosis. Building on these advancements, a multicenter, prospective, randomized controlled trial is proposed to evaluate the efficacy of sub-lobectomy in treating IDH wild-type/TERTp-mutant glioblastoma, aiming to improve evidence levels and establish standardized surgical practices for this devastating disease.

Conditions

Glioma; Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free Survival (PFS) in patients with IDH wild-type/TERTp-mutant glioblastoma in the sub-lobectomy group and in the imaging total resection (T1-enhanced border) group.

  From date of randomization until the date of first documented progression, assessed up to 36 months

Secondary Outcomes (1)

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 36 months

Other Outcomes (5)

• Postoperative quality of life

  up to 6 months

• Adverse effects

  up to 6 months

• Cognitive function

  up to 3 months

Study Arms (2)

The intervention group

EXPERIMENTAL

The intervention group was to receive frontal, temporal, parietal, and occipital sub-lobotomies that met anatomical criteria.

Procedure: sub-lobectomy

The control group

OTHER

The control group was to receive imaging total resection (T1-enhanced borders) that met RANO criteria.

Procedure: imaging total resection

Interventions

sub-lobectomy PROCEDURE

Combined with previous research and our team's precise neurosurgery concept, we define the surgical strategy based on lobectomy and further preserving the brain parenchyma in functional areas according to anatomical landmarks and electrophysiological boundaries as sub-lobectomy.

The intervention group

imaging total resection PROCEDURE

Imaging total resection (T1-enhanced borders) will met the RANO criteria

The control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible patients are aged between 18 and 80, have newly diagnosed high-grade diffuse adult-type gliomas, and have not received any other treatment besides puncture biopsy.
• Preoperative KPS score ≥70.
• Enhanced MRI can be tolerated.
• Sign the informed consent form.
• Patients with supratentorial gliomas and lesions confined to the unilateral frontal, temporal, parietal, and occipital lobes are included.
• Imaging total resection can be completed after preoperative imaging evaluation.
• The intraoperative integrative diagnosis was IDH wild-type high-grade glioma with TERT promoter mutation.

You may not qualify if:

• The tumor involves the anterior central gyrus, posterior central gyrus, nigral gyrus, limbic lobe, corpus callosum, basal ganglia, and lateral ventricles.
• The tumor involves 2 or more lobes of the brain;
• Developing severe systemic diseases such as renal insufficiency, hepatic insufficiency, cardiac insufficiency, etc.
• Previously, the patient had experienced other types of malignant tumours.
• Developing other brain diseases, such as Parkinson's or Alzheimer's disease.
• Simultaneously participating in other clinical trials.
• Expected survival is less than 3 months.
• Not receiving Stupp protocol after surgery.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (1)

Hushan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Related Publications (1)

• [1]. Weller M, Wick W, Aldape K, et al. Glioma. Nature Reviews Disease Primers 2015;1:15017. [2]. Schaff Lauren R,Mellinghoff Ingo K,Glioblastoma and Other Primary Brain Malignancies in Adults: A Review.[J] .JAMA, 2023, 329: 574-587. [3]. Xiong Z, Luo C, Wang P, Hameed NUF, Song S, Zhang X, Wu S, Wu J, Mao Y. The Intraoperative Utilization of Multimodalities Could Improve the Prognosis of Adult Glioblastoma: A Single-Center Observational Study. World Neurosurg. 2022 Sep;165:e532-e545. [4]. 罗宸, 吴帅, 吴劲松. 分子病理指导下的脑胶质瘤手术的研究进展.中华神经外科杂志, 2021, 37(9). 952-956. [5]. Halsted WS: I. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg 20:497-555,1894. [6]. Dandy WE: Removal of right cerebral hemisphere for certain tumors with hemiplegia. J Am Med Assoc 90:823-825, 1928. [7]. Li YM, Suki D, Hess K, Sawaya R: The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection? J Neurosurg 124:977-988, 2016. [8]. Molinaro Annette M,Hervey-Jumper Shawn,Morshed Ramin A et al. Association of Maximal Extent of Resection of Contrast-Enhanced and Non-Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma.[J] .JAMA Oncol, 2020, 6: 495-503. [9]. Roh Tae Hoon,Kang Seok-Gu,Moon Ju Hyung et al. Survival benefit of lobectomy over gross-total resection without lobectomy in cases of glioblastoma in the noneloquent area: a retrospective study.[J] .J Neurosurg, 2019, 132: 895-901. [10]de Leeuw CN, Vogelbaum MA. Supratotal resection in glioma: a systematic review. Neuro-Oncol. 2019;21(2):179-188. [11] Pessina F, Navarria P, Cozzi L, Ascolese AM, Simonelli M, Santoro A, Clerici E, Rossi M, Scorsetti M, Bello L. Maximize surgical resection beyond contrast-enhancing boundaries in newly diagnosed glioblastoma multiforme: is it useful and safe? A single institution retrospective experience. J Neurooncol. 2017 Oct;135(1):129-139. [12] Glenn CA, Baker CM, Conner AK, Burks JD, Bonney PA, Briggs RG, Smitherman AD, Battiste JD, Sughrue ME. An Examination of the Role of Supramaximal Resection of Temporal Lobe Glioblastoma Multiforme. World Neurosurg. 2018 Jun;114:e747-e755. [13] Salah M. Hamada, Ahmed H. Abou-Zeid. Anatomical resection in glioblastoma: extent of resection and its impact on duration of survival. 2016 The Egyptian Journal of Neurology, Psychiatry and Neurosurgery 1110-1083. [14] Di L, Shah AH, Mahavadi A, Eichberg DG, Reddy R, Sanjurjo AD, Morell AA, Lu VM, Ampie L, Luther EM, Komotar RJ, Ivan ME. Radical supramaximal resection for newly diagnosed left-sided eloquent glioblastoma: safety and improved survival over gross-total resection. J Neurosurg. 2022 May 27;138(1):62-69. [15] Schneider M, Potthoff AL, Keil VC, Güresir Á, Weller J, Borger V, Hamed M, Waha A, Vatter H, Güresir E, Herrlinger U, Schuss P. Surgery for temporal glioblastoma: lobectomy outranks oncosurgical-based gross-total resection. J Neurooncol. 2019 Oct;145(1):143-150. [16] Shah AH, Mahavadi A, Di L, Sanjurjo A, Eichberg DG, Borowy V, Figueroa J, Luther E, de la Fuente MI, Semonche A, Ivan ME, Komotar RJ. Survival benefit of lobectomy for glioblastoma: moving towards radical supramaximal resection. J Neurooncol. 2020 Jul;148(3):501-508. [17]. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology 2021;23:1231-51. [18]. Killela PJ, Reitman ZJ, Jiao Y, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 2013;110:6021-6. [19]. Ellingson BM, Wen PY, Cloughesy TF. Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials. Neurotherapeutics. 2017 Apr;14(2):307-320.

  BACKGROUND

MeSH Terms

Conditions

Glioma; Glioblastoma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This study employed a single-blind approach whereby the participants were unaware of the kind of surgical resection they were receiving.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Model Details: Type of study: randomized parallel controlled, open-label, multicenter clinical trial. Interventions: the intervention group was to receive frontal, temporal, parietal, and occipital sub-lobotomies that met anatomical criteria, and the control group was to receive imaging total resection (T1-enhanced borders) that met the Response Assessment in Neuro-Oncology (RANO) criteria. Randomization The control group and intervention group were equal in size. Following intraoperative pathological diagnosis, participants were randomly assigned using a centralized randomization system known as the Interactive Web Response System (IWRS). Stratification factors included preoperative age brackets of \[18-65\] and (65-80), gender (male or female), and tumor site in the frontal, temporal, parietal, and occipital lobes.

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: April 16, 2024
• Study Start: April 8, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 16, 2024

Record last verified: 2024-04

Locations

CN (1)