Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioma

Brain Neoplasms

Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Molgramostim

Sargramostim

Temozolomide

Immunomodulating Agents

Monatide (IMS 3015)

Antineoplastic Agents, Alkylating

Alkylating Agents

PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.

PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.

PEPIDH1M vaccine

After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.

Tetanus-Diphtheria Toxoid (Td)

Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.

Katherine Peters, M.D., Ph.D.

Potential subjects with progressive Grade II primary brain tumor that have IDH1 positive testing from the primary tumor (initial diagnosis) will be offered this treatment study in order to test the safety of the PEPIDH1M vaccine in combination with standard chemotherapy (temozolomide).

After informed consent has been signed, subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen.

Eligible subjects will undergo a 1-2 hour leukapheresis (to pull off white blood cells) for immune monitoring. Within 48 hours of leukapheresis, subjects will receive vaccine site pre-conditioning as a single dose of Td toxoid (in a total volume of 0.4 mLs salt water/saline) given in the intradermal space (just under the surface of the skin) to the right groin area. The pre-conditioning will be administered one day prior to receiving PEPIDH1M vaccine. The peptide vaccine is administered in the upper thigh area approximately 4 inches below the groin in the intradermal space as vaccine # 1. Subsequent vaccines will be given on day 15 ±3 days (vaccine #2) and day 29 ±3 days (vaccine #3). Each injection of the peptide vaccine will be given half on the right groin and half on the left groin. The first 3 peptide vaccine injections will occur without temozolomide (standard of care chemotherapy).

Seven to twelve days after the 3rd vaccine, subjects will have standard of care surgery to remove the tumor. Tumor samples will be evaluated for the IDH1 markers and analyzed for other cells that may have entered the tumor.

Based on the the tissue obtained at surgery, subjects with stable histologic grade at recurrence will then be treated with vaccine and temozolomide. During monthly cycles of temozolomide, subjects will receive the vaccine on day 22 (+ 2 days) for a maximum of 15 total vaccines (which includes the first 3 bi-weekly vaccines). Patients that have transitioned to a higher grade brain tumor at the time of surgery will receive temozolomide and radiation therapy per standard of care and monthly vaccines (vaccines #4-6). After completion of radiation therapy, subjects in this treatment group will receive vaccines monthly on day 22 (+2 days) with post-RT cycles of TMZ to a maximum of 15 vaccines.

All Adverse Events will be collected from time of consent until off study. The treatment phase of the study will end 1 month after the last vaccine. Patients will be followed only for overall survival, progression-free survival, and subsequent therapies thereafter.

Subjects will have blood collected for immune monitoring and biomarker testing during the following times: prior to initiating vaccine therapy (at the leukapheresis visit), prior to surgery to remove the tumor, at the clinic visit prior to starting first cycle of temozolomide after surgery (or radiation therapy and temozolomide for those who transition to higher grade), at vaccine #6, and at end of vaccine treatment (1 month after vaccine #15 or time the subject comes off study, whichever comes first).

Subjects will be imaged with contrast-enhanced magnetic resonance imaging (MRI) according to standard of care every 10 weeks (+/- 4 weeks) while on temozolomide and afterward, per the treating neuro-oncologist's recommendation. Revised Assessment in Neuro-Oncology (RANO) criteria will be used for assessment of pseudoprogression and tumor progression. Subjects demonstrating definitive progression will be removed from study.

As part of standard care for these subjects, upon tumor progression, participants may undergo biopsy or resection. As this is not a research procedure, consent will be obtained separately. Subjects that have this procedure done within the Duke University Health System will be asked to have a portion of the tumor sample, if possible, to assess immunologic cell infiltration, antigen expression, and biomarkers for immunologic response.

Please note, data collection will continue to occur outside of the defined primary and secondary outcomes for exploratory objectives.

The specific exploratory objective involves describing the progression free survival (PFS) and overall survival (OS). The endpoint is the proportion of patients alive without disease progression 6 months after initial vaccine treatment, and both the median PFS, and the median OS.

The objective will be reviewed at 3 years after the last subject came off study.

IDH1 Peptide Vaccine for Recurrent Grade II Glioma

Patients With IDH1 Positive Recurrent Grade II Glioma Enrolled in a Safety and Immunogenicity Study of Tumor-Specific Peptide Vaccine

The percentage of patients who experience an unacceptable toxicity defined as any Grade 3 toxicity at least possibly attributed to the vaccine (or vaccine + TMZ and/or RT) that does not resolve to baseline within 3 weeks, any Grade 3 hypersensitivity reactions requiring steroids, any Grade 4 toxicity, including neurologic events not due to progressive disease, or any life threatening-event not attributable to concomitant medication, co-morbid event, or disease progression.

Assess the immunogenicity of the PEPIDH1M vaccine with adjuvant TMZ using ELISpot. This will be done by finding the difference between the number of SFC after 3 post-surgery vaccines and the number of SFC at baseline for each evaluable subject. Immunogenicity will then be summarized by the percentage of evaluable subjects who have a positive vaccine response after 3 post-surgery vaccines. A response will be considered positive if the difference in SFC measurement is greater than 20 SFC per 10\^6 lymphocytes after determining the level of detection in the IDH ELISpot.

Katy Peters, MD, PhD

Associate Professor, Neurology and Neurosurgery

PEPIDH1M vaccine is made up of a peptide that spans the mutated region of IDH1R132H (Isocitrate Dehydrogenase 1). The peptide is administered with GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51.

PEPIDH1M vaccine: PEPIDH1M vaccine is made up of 500 µg of 25 amino acid peptide administered with 150 µg of GM-CSF mixed 1:1 with Montanide ISA 51 administered intradermally. The peptide vaccine is administered in the groin area approximately 10 cm below the inguinal ligament.

Tetanus-Diphtheria Toxoid (Td): After consent has been signed, all subjects will undergo standard of care vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Within 48 hours of leukapheresis, subjects will receive a vaccine site pre-conditioning as a single dose of Td toxoid (1 flocculation unit, Lf, in a total volume of 0.4 mLs saline) administered intradermally to the right side of the groin one day prior to receiving the first PEPIDH1M vaccine.

Temozolomide: Subjects are treated with temozolomide (TMZ) at a targeted dose of 50-100mg/m2/d for 21 days every 28 days for up to 12 cycles. Subjects that have transitioned to a higher grade brain tumor at time of surgery will receive TMZ and radiation therapy per standard of care before starting TMZ cycles.

PEPIDH1M Vaccine

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Katy Peters, M.D., Ph.D.

Percentage of Participants With an Unacceptable Toxicity

Only 21 of the 24 overall study patients made it far enough on the study to receive 3 post-surgery vaccines and become evaluable for this outcome.

Percentage of Patients With a Positive Vaccine Response After 3 Post-Surgery Vaccines as Measured by IFNγ ELIspot

Overall Study

Nausea

Vomiting

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Signs and Symptoms, Digestive

Acute Graft Versus Host Disease

Neuroepithelioma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Bevacizumab

Irinotecan

Dexamethasone

Palonosetron

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Serotonin

Serotonin 5-HT3 Receptor Antagonists

Neurotransmitter Agents

single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.

Palonosetron (Aloxi) and Dexamethasone

Mary Lou Affronti, RN, MSN, ANP

1. Primary Objective:

   * To determine the efficacy and tolerability of palonosetron and dexamethasone in preventing acute CINV in brain tumor patients during the first 24 hours of receiving Irinotecan /Bevacizumab regimens.
2. Secondary Objective

   * To determine the safety and tolerability of palonosetron in brain tumor patients.
   * To determine the effects of glucocorticoid and anticonvulsants on the efficacy of palonosetron.
   * To determine the efficacy of palonosetron and dexamethasone in preventing delayed CINV in brain tumor patients during days 2-5.
   * To determine if patients receiving palonosetron have less fatigue than baseline.

Before the patients receive the palonosetron, a physical exam and blood tests are performed to determine eligibility. If eligible and willing, subjects are given Palonosetron intravenously. Subjects are given the Palonosetron and Dexamethasone 30 minutes before the first dose of Irinotecan and Bevacizumab chemotherapy. The total expected duration of participation is 57 days. Subjects are also asked to complete 4 questionnaires about nausea and vomiting, as well as daily functioning and fatigue. Subjects are asked to complete these questionnaires before starting chemotherapy, the day of starting chemotherapy and for the next 4 days after receiving chemotherapy, for a total of 6 times. Subjects are asked to complete this set of questionnaires each of the 3 times that they receive chemotherapy during the 6-week treatment cycle.

The other treatments subjects would normally receive for their brain tumor and their routine care are not affected by the study.

Aloxi for Prevention of Chemotherapy Induced Nausea and Vomiting in Malignant Glioma Patients Receiving Irinotecan With Bevacizumab

A Phase II Single Arm Trial of Palonosetron (PALO) for the Prevention of Acute and Delayed Chemotherapy Induced Nausea and Vomiting (CINV) in Malignant Glioma (MG) Patients Receiving Irinotecan in Combination With Bevacizumab

Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.

Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during days 2 through 5 of chemotherapy treatment during the first cycle of treatment

Percentage of patients with ≥ grade 3, treatment-related toxicities using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue.

Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from the mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue. Acute CINV complete response (CR) is defined as not having an emetic episode or any use of antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment.

Eisai Inc.

National Institute of Neurological Disorders and Stroke (NINDS)

Duke University

The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Patient receives IV Aloxi

Palonosetron (Aloxi) and Dexamethasone: single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.

Patient Receives IV Aloxi

Mary Lou Affronti

Intent-to-treat; 11 patients did not complete the study measure for day 1 of the first week of chemotherapy

Acute CINV (Chemotherapy Induced Nausea and Vomiting) CR (Complete Response) Rate

corticosteroid used at baseline

no corticosteroid used at baseline

Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Corticosteroid Use at Baseline

anticoagulant used at baseline

no anticoagulant used at baseline

Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Anticoagulant Use at Baseline

Intent-to-treat; 10 patients did not complete the study measure for days 2-5 of the first week of chemotherapy

Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate

Percentage of Patients With ≥ Grade 3, Treatment-related Toxicities

Intent-to-treat; 16 patients did not complete the study measure at baseline or on day 5 of the first week of chemotherapy

Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy

Not CR

Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy by Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR)

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Esophageal Neoplasms

Prostatic Neoplasms

Neoplasm Metastasis

Rectal Neoplasms

Hypoxia

Neoplastic Processes

Signs and Symptoms, Respiratory

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Esophageal Cancer

Anti-Obesity Agents

Vasoconstrictor Agents

Respiratory System Agents

Imidazole

Phenylpropanolamine

Guaifenesin

Chlorpheniramine, phenylpropanolamine drug combination

Enzyme Inhibitors

Injection with the hypoxia tracer \[18F\]HX4 and PET imaging at baseline for esophageal, rectal, prostate cancer, primary brain tumor (grade IV glioma) and brain metastases and after 2 weeks of radiotherapy for esophageal, rectal and brain metastases

The \[18F\]HX4 PET scan will be performed, by administrating 444 MBq (12 mCi) \[18F\]HX4 via a bolus IV injection.

Injection with the hypoxia tracer [18F]HX4,

Philippe Lambin, Prof. dr.

Regulation of tissue oxygen homeostasis is critical for cell function, proliferation and survival. Evidence for this continues to accumulate along with our understanding of the complex oxygen-sensing pathways present within cells. Several pathophysiological disorders are associated with a loss in oxygen homeostasis, including heart disease, stroke, and cancer. The microenvironment of tumors in particular is very oxygen heterogeneous, with hypoxic areas which may explain our difficulty treating cancer effectively. Prostate carcinomas are known to be hypoxic. Increasing levels of hypoxia within prostatic tissue is related to increasing clinical stage, patient age and a more aggressive prostate cancer. Several researches indicated that hypoxia might also play a role in esophageal cancer. In glial brain tumors, hypoxia is correlated with more rapid tumor recurrence and the hypoxic burden in newly diagnosed glioblastomas is linked to the biological aggressiveness. In brain metastases CA-IX expression (a marker for hypoxia) is correlated to the primary non-small cell lung carcinomas. Hypoxia enhances proliferation, angiogenesis, metastasis, chemoresistance and radioresistance of hepatocellular carcinoma. The hypoxic markers HIF-1α, VEGF, CA-IX and GLUT-1 were all over expressed in colorectal cancer and its liver metastases. Based on literature, hypoxia in tumors originating or disseminated to prostate, esophagus, brain and rectum cancer will be studied in this trial.

Rationale: Non-invasive imaging of hypoxia with the aid of PET-scans could help to select the patients having a hypoxic tumor, who could be treated with specific anti-hypoxic treatments. The added value of additional anti-hypoxic treatments depends on the presence of hypoxia and adequate patient selection. Several 2-nitroimidazoles, labeled with Fluor-18 (18F) have already been used in patients to identify hypoxia. However, suboptimal image quality and unpredictable kinetics limit their use. In extensive pre-clinical models and clinical trials the combination of HX4 labeled with 18F showed to be a promising and non-toxic new probe to determine hypoxia. With this tracer the proportion of hypoxic tumors in several cancer types will be verified.

Objective: Determine if tumor hypoxia can be accurately visualized with \[18F\]HX4 in solid lesions.

Study design: Phase II, several solid tumors, single-centre, imaging, non-randomized, open label trial.

Study population:

Main patient characteristics are:

* Histological/cytological confirmed carcinoma of de esophagus, rectum or prostate or radiological suspicion for Grade IV glioma (primary brain tumor) or brain metastases.
* WHO performance status 0 to 2
* Adequate renal function (calculated creatinine clearance at least 60 ml/min).
* Capable of complying with study procedures

Main intervention: In addition to standard clinical care patients receive two additional PET scans after injection with the hypoxia tracer \[18F\]HX4.

Main study parameters/endpoints:

* Visualization and quantification of tumor hypoxia with \[18F\] HX4 PET imaging
* Exploring the potential relationship between \[18F\] HX4 uptake with local and locoregional tumor recurrence and survival
* Correlation of hypoxia imaging with blood hypoxia markers
* Correlation of hypoxia imaging with tumor tissue biomarkers
* Evaluation of tumor hypoxia changes during treatment.
* Spatial correlation of \[18F\] HX4-PET with imaging pre-treatment (if present from routine clinical practice)
* Spatial correlation of \[18F\] HX4-PET with imaging three months after treatment (if present from routine clinical practice)
* Quantitative and qualitative correlation of \[18F\] HX4-PET obtained before treatment and two weeks into treatment

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The radiation burden due to \[18F\]HX4 is similar to that encountered in many routine nuclear medicine procedures e.g. \[18F\]FDG PET. Administration of \[18F\]HX4 presents no known risks. In previous studies (healthy volunteers, phase I, phase II) no adverse effects were observed. There are no immediate potential benefits except the satisfaction to participate to improve of knowledge.

Tumor Hypoxia With HX4 PET in Several Diseases

Non-invasive Imaging of Tumor Hypoxia With [18F]HX4 Positron-Emission-Tomography (PET): A Phase II Trial

Visualization of tumor hypoxia with \[18F\] HX4 PET imaging

Quantification of tumor hypoxia with \[18F\] HX4 PET imaging

Exploring the potential relationship of \[18F\] HX4 uptake with local and locoregional tumor recurrence and survival

Correlation of hypoxia imaging with blood hypoxia markers

Correlation of hypoxia imaging with tumor tissue biomarkers

Evaluation of tumor hypoxia changes during treatment

Spatial correlation of \[18F\] HX4-PET with imaging pre-treatment (if present from routine clinical practice); performed by a rigid registration of the scans and a voxel wise comparison of the uptake within the tumor

Spatial correlation of \[18F\] HX4-PET with imaging three months after treatment (if present from routine clinical practice), performed by a rigid registration of the scans and a voxel wise comparison of the uptake within the tumor

Maastricht Radiation Oncology

Behaviors and Mental Disorders

Glioblastoma

Disease Progression

Astrocytoma

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
IDH1 Peptide Vaccine for Recurrent Grade II Glioma	NCT02193347	Brain Cancer Brain Neoplasm,... Brain Neoplasms... Brain Tumor Cancer of the B...	PEPIDH1M vaccin... Tetanus-Diphthe... Temozolomide	18 Years -	Duke University
Aloxi for Prevention of Chemotherapy Induced Nausea and Vomiting in Malignant Glioma Patients Receiving Irinotecan With Bevacizumab	NCT00636805	Brain Cancer	Palonosetron (A...	18 Years -	Duke University
Tumor Hypoxia With HX4 PET in Several Diseases	NCT02584400	Prostatic Neopl... Esophageal Neop... Neoplasm Metast... Rectal Neoplasm... Brain Neoplasm,...	Injection with ...	18 Years -	Maastricht Radiation Oncology
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
IDH1 Peptide Vaccine for Recurrent Grade II Glioma	NCT02193347	Brain Cancer Brain Neoplasm,... Brain Neoplasms... Brain Tumor Cancer of the B...	PEPIDH1M vaccin... Tetanus-Diphthe... Temozolomide	18 Years -	Duke University

Spots Global Cancer Trial Database for brain neoplasm, primary