Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anaplastic Astrocytoma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Natriuretic Agents

Cetuximab

Mannitol

Antineoplastic Agents, Immunological

Diuretics

Mannitol 20% 12.5ml over two minutes for blood brain barrier (BBB) disruption followed by Cetuximab administered intra-arterially for three doses at a dose of 250 mg/m2 combined with hypofractionated re-irradiation

Intra-arterial Cetuximab

Intra-arterial Mannitol

Hypofractionated re-irradiation

John Boockvar, MD

Tamika Wong, MPH

David Langer, MD

Rafael Ortiz, MD

Alexis Demopoulos, MD

Jed Pollack, MD

Anuj Goenka, MD

Sherese Fralin, NP

Ashley Ray, NP

Karissa Tan, NP

Primary brain tumors are typically treated by surgery, radiation therapy and chemotherapy, either individually or in combination. Present therapies are inadequate, as evidenced by the low 5-year survival rate for brain cancer patients, with median survival at approximately 12 months. Glioma is the most common form of primary brain cancer, afflicting approximately 7,000 patients in the United States each year. These highly malignant cancers remain a significant unmet clinical need in oncology. GBM often has a high expression of EFGR (Epidermal Growth Factor Receptor), which is associated with poor prognosis. Several methods of inhibiting this receptor have been tested, including monoclonal antibodies, vaccines, and tyrosine kinase inhibitors. The investigators hypothesize that in patients with recurring GBM, intracranial superselective intra-arterial infusion of Cetuximab (CTX), at a dose of 250mg/m2 in conjunction with hypofractionated radiation, will be safe and efficacious and prevent tumor progression in patients with recurrent, residual GBM.

Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA

Phase II Trial of Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory Glioblastoma Multiforme, Anaplastic Astrocytoma, and Anaplastic Oligoastrocytoma

The 6-month PFS will be estimated by calculating the proportion of patients who are alive at 6 months from treatment commencement and are progression-free.

OS will be calculated as the time from treatment initiation to the date of death.

Subjects will be classified according to the RECIST criteria, which is a composite of MRI changes, clinical response and changes in steroid use.

Toxicities will be tabulated and graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03

Northwell Health

Principal Investigator

Behaviors and Mental Disorders

Disease Progression

Quality of Life

Supramaximal resection: maximal resection of the contrast-enhancing and non-contrast-enhancing part of the tumor (FLAIRectomy)

Maximal safe resection of the contrast-enhancing part of the tumor

Supramaximal resection. Tumor resection continues until either the FLAIR abnormalities have been resected based on the neuronavigation (after updating the navigation intraoperatively), or when subcortical tracts are identified with intraoperative stimulation.

Supramaximal resection

Maximal safe resection. Tumor resection continues until maximal safe resection has been achieved as by the neurosurgeon's opinion.

Maximal safe resection

Jasper Gerritsen, MD PhD

Arnaud Vincent, MD PhD

Mitchel Berger, MD

Brian Nahed, MD

Steven De Vleeschouwer, MD PhD

Christine Jungk, MD PhD

Sandro Krieg, MD MBA

Arthur Wagner, MD PhD

Marike Broekman, MD PhD

Philippe Schucht, MD PhD

A greater extent of resection of the contrast-enhancing (CE) tumor part has been associated with improved outcomes in high-grade glioma patients. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in HGG patients in terms of survival, functional, neurological, cognitive, and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively.

This study is an international, multicenter, prospective, 2-arm cohort study of observational nature. Consecutive HGG patients will be operated with supramaximal resection or maximal resection at a 1:3 ratio. Primary endpoints are: 1) overall survival and 2) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months, and 6 months postoperatively. Secondary endpoints are 1) residual CE and NCE tumor volume on postoperative T1-contrast and FLAIR MRI scans 2) progression-free survival; 3) onco-functional outcome, and 4) quality of life at 6 weeks, 3 months, and 6 months postoperatively.

The study will be carried out by the centers affiliated with the European and North American Consortium and Registry for Intraoperative Mapping (ENCRAM).

This is an international, multicenter, prospective, observational, 2-arm cohort study (registration: clinicaltrials.gov ID number TBA). Eligible patients are operated with supramaximal resection versus maximal resection with a 1:3 ratio with a sequential computer-generated random number as subject ID. Intraoperative mapping techniques and/or surgical adjuncts can be used in both treatment arms to ensure the safety of the resection (to minimize the risk of postoperative deficits). Supramaximal resection is defined as 0 cm3 CE tumor and 5 cm3 or less NCE tumor, whereas maximal resection is defined as 0 cm3 CE tumor and \>5 cm3 NCE tumor (in line with the updated RANO criteria).

Study patients are allocated to either the supramaximal or maximal safe resection group and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) scale. Language function will be evaluated using a standard neurolinguistic test-battery consisting of the Aphasia Bedside Check (ABC), Shortened Token test, Verbal fluency, Picture description and Object naming. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system. Health-related quality of life (HRQoL) will be assessed with the EORTC QLQ C30, EORTC QLQ BN20 and EQ 5D questionnaires. Overall survival and progression-free survival will be assessed. We expect to complete patient inclusion in 4 years. The estimated duration of the study (including follow-up) will be 5 years.

The primary study objective is to evaluate the safety and efficacy of supramaximal resection versus safe maximal resection in HGG patients as measured by overall survival (OS) and postoperative NIHSS deterioration. Secondary study objectives are to evaluate extent of resection of CE and NCE tumor, quality of life, progression-free survival (PFS), onco-functional outcome (OFO), and SAEs after SMR or maximal safe resections as measured by volumetric analyses of contrast-enhanced MRI images with gadolinium combined with FLAIR images, tumor progression on MRI scans, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ 5D), combining postoperative residual volume with NIHSS outcomes, and recording SAEs respectively.

Patients will be recruited from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals, located in Europe and the United States. The study is carried out by centers from the ENCRAM Consortium.

The SUPRAMAX Study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)

The SUPRAMAX-study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)

Time from diagnosis to death from any cause

NIHSS deterioration of 1 point or more at 6 weeks after surgery

NIHSS deterioration of 1 point or more at 3 months after surgery

NIHSS deterioration of 1 point or more at 6 months after surgery

Time from diagnosis to disease progression (occurrence of a new tumor lesions with a volume greater than 0.175 cm3, or an increase in residual tumor volume of more than 25%) or death, whichever comes first

Residual tumor volume of the contrast-enhancing and non-contrast enhancing part, as assessed by a neuroradiologist on postoperative MRI scan (T1 with contrast and FLAIR sequences) using manual or semi-automatic volumetric analyses (Brainlab Elements iPlan CMF Segmentation, Brainlab AG, Munich, Germany; or similar software)

According to the OFO classification, consisting of the combination of presence/absence of functional deterioration with gross-total resection

Quality of life as assessed by the EORTC QLQ C30 questionnaire

Quality of life as assessed by the EORTC QLQ BN20 questionnaire

Quality of life as assessed by the EQ-5D questionnaire

Serious Adverse Events within 6 weeks postoperatively

Haaglanden Medical Centre

Universitaire Ziekenhuizen KU Leuven

University Hospital Heidelberg

Technical University of Munich

Insel Gruppe AG, University Hospital Bern

Massachusetts General Hospital

University of California, San Francisco

Jasper Gerritsen

Mitogens

Mannitol 20% 12.5ml over two minutes for Blood Brain Barrier (BBB) disruption followed by CTX administered intra-arterially for three doses at a dose of 250mg/m2

Christopher Filippi, MD

Shamik Chakraborty, MD

Primary brain cancer kills up to 10,000 Americans a year. These brain tumors are typically treated by surgery, radiation therapy and chemotherapy, either individually or in combination. Present therapies are inadequate, as evidenced by the low 5-year survival rate for brain cancer patients, with median survival at approximately 12 months. Glioma is the most common form of primary brain cancer, afflicting approximately 7,000 patients in the United States each year. These highly malignant cancers remain a significant unmet clinical need in oncology. GBM often has a high expression EFGR (Epidermal Growth Factor Receptor) which is blocked by Cetuximab (CTX). The investigators have recently completed a separate Phase I clinical trial using superselective intra-arterial cerebral infusion (SIACI) of CTX after blood brain barrier disruption (BBBD) for recurrent GBM (Chakraborty et al, in revision, Journal of Neurooncology). The investigators found that intra-arterial infusion of CTX is well tolerated with few adverse effects. The investigators hypothesize that in patients with newly diagnosed GBM, repeated SIACI of this drug after BBBD will be safe and efficacious for our patients when combined with standard chemoradiation (STUPP protocol).

This trial will be a non-randomized open label Phase I/II clinical trial. In addition to standard chemotherapy and radiation therapy (STUPP protocol) the patient will be given CTX intra-arterially after BBBD for a total of three doses at approximately post surgery days 30, 120 and 210.

Super-selective Intra-arterial Repeated Infusion of Cetuximab for the Treatment of Newly Diagnosed Glioblastoma

Phase I/II Trial of Super-selective Intra-arterial Repeated Infusion of Cetuximab for the Treatment of Newly Diagnosed Glioblastoma

Subjects will be classified according to the RANO criteria, which is a composite of MRI changes, clinical response and changes in steroid use.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA	NCT02800486	Glioblastoma Anaplastic Astr... Anaplastic Olig... Glioma Brain Neoplasm Brain Cancer Brain Tumor Brain Tumor, Re... Brain Neoplasm,...	Intra-arterial ... Intra-arterial ... Hypofractionate...	18 Years -	Northwell Health
The SUPRAMAX Study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)	NCT06118723	Glioblastoma High-grade Glio... Glioblastoma, I... Glioblastoma, I... Glioblastoma Mu... Astrocytoma, Gr... Astrocytoma, Gr... Astrocytoma, Ma... Brain Neoplasms Brain Neoplasm,... Brain Neoplasms... Brain Neoplasm,...	Supramaximal re... Maximal safe re...	18 Years - 90 Years	Erasmus Medical Center
The SUPRAMAX Study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)	NCT06118723	Glioblastoma High-grade Glio... Glioblastoma, I... Glioblastoma, I... Glioblastoma Mu... Astrocytoma, Gr... Astrocytoma, Gr... Astrocytoma, Ma... Brain Neoplasms Brain Neoplasm,... Brain Neoplasms... Brain Neoplasm,...	Supramaximal re... Maximal safe re...	18 Years - 90 Years	Erasmus Medical Center
Super-selective Intra-arterial Repeated Infusion of Cetuximab for the Treatment of Newly Diagnosed Glioblastoma	NCT02861898	Glioblastoma Brain Cancer Brain Neoplasm Brain Tumor Brain Neoplasm,... EGFR Gene Overe... GBM	Intra-arterial ... Intra-arterial ...	18 Years -	Northwell Health
Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA	NCT02800486	Glioblastoma Anaplastic Astr... Anaplastic Olig... Glioma Brain Neoplasm Brain Cancer Brain Tumor Brain Tumor, Re... Brain Neoplasm,...	Intra-arterial ... Intra-arterial ... Hypofractionate...	18 Years -	Northwell Health

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