Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Brain Neoplasms

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Molgramostim

Sargramostim

Temozolomide

Rindopepimut

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunologic Factors

Antineoplastic Agents, Immunological

Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance.

Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM CSF.

Rindopepimut (CDX-110) with GM-CSF

150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression.

Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8mL containing approximately 100mcg of KLH.

This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer.

All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin.

Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival.

The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used chemotherapy drug temozolomide can help improve the life expectancy of patients with newly diagnosed, resected EGFRvIII positive glioblastoma.

The duration of participation in this study may be up to 5 years. After you are screened and enrolled in the study, you will be administered temozolomide and either rindopepimut/GM-CSF or KLH until either disease progression or intolerance to the medications. If your tumor progresses while on this study, your doctor may treat you with other therapies that are not part of the study.

Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma

An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma

The primary efficacy endpoint of Overall Survival is defined as the number of months from randomization to the date of death (whatever the cause), and will be censored for patients who remain alive at completion of the study for patients with a gross total resection (\~n=374). The overall survival of patients will be monitored and compared between the two study arms until the end of the study.

Compare progression-free survival between the two treatment arms

Safety and tolerability will be measured by comparing the two arms in regards to vital sign measurement, physical and neurological examination, adverse events reporting, ECOG performance status, and EORTC core Quality of Life Questionnaire

Celldex Therapeutics

Symptoms and General Pathology

Recurrence

Anaplastic Astrocytoma

Antibodies

Immunoglobulins

Mitogens

AMG 595

Immunoconjugates

Pre-specified nominal doses are proposed in the dose exploration. Intermediate doses may also be used if required based on the CRM design.

Dose selected from Part 1 dose exploration

AMG 595 is an antibody drug conjugate that binds to EGFRvIII.

This is an open-label, sequential dose exploration study of single agent AMG 595 administered in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA). The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics (PK) of AMG 595, and also to evaluate the objective response rate in subjects receiving AMG 595. This study will be conducted in two parts. Part 1 will explore doses of AMG 595 in subjects with recurrent GBM and/or AA. Part 2 (dose expansion) will examine the MTD established in Part 1 in subjects with recurrent GBM.

This study of AMG 595 will be conducted in two parts: Part 1 (dose exploration) and Part 2 (dose expansion). Part 1 of the study is in subjects with recurrent glioblastoma multiforme (GBM) and/or anaplastic astrocytomas (AA), and Part 2 is examining the MTD in subjects with recurrent GBM. Approximately 30-40 subjects may be enrolled in Part 1, and up to 36 subjects may be enrolled in Part 2. The dose of AMG 595 utilized in Part 2 will be dependent upon data obtained in Part 1 of the study.

AMG 595 First-in-Human in Recurrent Gliomas

A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 595 in Subjects With Recurrent Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)

Amgen

Natriuretic Agents

Cetuximab

Mannitol

Intraarterial Mannitol 25% 3-10 ml to open the blood brain barrier followed by Intraarterial Cetuximab single dose (starting at 100mg/m2 and escalating up to 500mg/m2)

Superselective Intraarterial Cerebral Infusion of Cetuximab

John Boockvar, MD

The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. Initial therapy consists of either surgical resection, external beam radiation or both. All patients experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). Superselective Intraarterial Cerebral Infusion (SIACI) is a technique that can effectively increase the concentration of drug delivered to the brain while sparing the body of systemic side effects. One currently used drug called, Cetuximab (Erbitux) has been shown to be active in human brain tumors but its actual CNS penetration is unknown. This phase I clinical research trial will test the hypothesis that Cetuximab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 500mg/m2 to ultimately enhance survival of patients with relapsed/refractory GBM/AA. By achieving the aims of this study the investigators will determine the the toxicity profile and maximum tolerated dose (MTD) of SIACI Cetuximab. The investigators expect that this study will provide important information regarding the utility of SIACI Cetuximab therapy for malignant glioma, and may alter the way these drugs are delivered to the investigators patients in the near future.

There is no current standard of care for recurring GBM after patients receive Bevacizumab (Avastin) intravenously (IV) at 10mg/kg with CPT-11 (Irinotecan). At that point, these patients are deemed treatment failures and are given another experimental treatment. Because of the blood brain barrier (BBB) where IV drugs do not penetrate the blood vessel walls well to get into the brain, no one knows for sure if these IV drugs actually get into the brain after infusion. Previous studies have shown that if you want to increase your penetration of drug to the brain, that intra-carotid artery (intraarterial) delivery is superior to standard intravenous delivery. Previous techniques using intraarterial (intracarotid) infusion still were non-selective as drug delivery still went to all blood vessels in the brain, so patients still had significant adverse events, such as blindness. Newer techniques in interventional neuroradiology have allowed for a more selective delivery of catheters higher up into the arterial tree where agents such as chemotherapies, can be delivered without the risk of adverse affects such as blindness. In fact, studies here at Cornell have developed very new and exciting super selective intraarterial delivery treatments for Retinoblastoma, eye tumors with little toxicity and a clinical trial of intraarterial delivery of Avastin is currently underway for GBM. Therefore, this trial will ask one simple question: Is it safe to deliver a dose of Cetuximab intraarterially using these super selective delivery techniques instead of the standard intravenous route of administration? This should not only increase the amount of drug that gets to the tumor but also spare the patient any adverse effects from a less selective delivery. Prior to that single dose of intraarterial Cetuximab, the patient will also receive a dose of mannitol that opens up the blood brain barrier to improve delivery of the agent to the brain. After that single dose of Mannitol and Cetuximab intraarterially, the patient will be evaluated for 4 weeks to assess for toxicity. After this point, the patient is done with the "experimental" aspects of the protocol. If no toxicity at this point, then the patient will go on and get their chosen chemotherapy as determined by their treating oncologist. In summary, this is a Phase I trial that is designed to test the safety of a single dose of intraarterial delivery of Mannitol and Cetuximab , prior to starting the patients next round of chosen chemotherapy

To summarize:

Current Standard of Care Therapy : None

Experimental portion of this proposal:

Day 0: Intraarterial Mannitol to open the blood brain barrier followed by Intraarterial Cetuximab single dose (starting at 100mg/m2 and up to 500mg/m2)

Therefore the experimental aspects of this treatment plan will include:

1. Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol 25%; 3-10 mL/s for 30seconds) in order to disrupt the blood brain barrier. This technique has been used in several thousand patients in previous studies for the IA delivery of chemotherapy for malignant glioma.
2. To add a single intraarterial delivery (SIACI) of the Cetuximab for patients with recurring or relapsing high grade glioma. After a one cycle observation period to assess for toxicity from the IA infusion, the subject will receive a regimen of chemotherapy to be decided by their treating oncologist The dose escalation algorithm is as follows: We will use a single intracranial superselective intraarterial infusion of Cetuximab, starting at a dose of 100mg/m2 in the first three patients. Assuming no dose limiting toxicity during the next 28 days after the infusion, the patient will then begin their standard chemotherapy regimen which is to be determined by their treating oncologist. The doses will be escalated from 100, to 200, 300, 400 and finally 500mg/m2 in this Phase I trial.

Both hematologic and non-hematologic toxicity from the IA infusion of Cetuximab will be determined and scored according to the NCI Common Toxicity Criteria (version 3.0). Monitoring will also include an MRI of the brain at 4 weeks post infusion.

Most patients with GBM are also monitored every two months with serial history, neurological and physical examinations together with serial blood counts, prothrombin time (PT), partial thromboplastin time (PTT) and chemistries. In addition, most patients with GBM have an MRI performed every two cycles or approximately every two months to assess for tumor progression. .

Since this is a Phase I trial, response is not a primary endpoint of the trial. However, we will evaluate response to the one time IA Cetuximab therapy with a a MRI with the injection of contrast about 4 weeks after infusion. Follow-up of all patients in the trial regardless of the chemotherapy regimen they try after the IA Cetuximab therapy will continue until disease progression or death. Survival will be measured from the time of the dose of IA Cetuximab®. We expect patients in the trial to monitored for 12 months.

This treatment may be harmful to a fetus . female subjects of childbearing age, will be asked to practice birth control methods while participating in this research study and for 3 months following her treatment. These methods include oral contraceptives, contraceptive shots, and barrier methods, such as condom use, sponges, and diaphragms. Fertile males are required to use these barrier methods.

The patient may be responsible for any additional costs associated with enrollment in the trial. All costs of the IA delivery and the cost of the drug will be submitted to the patient's insurance provider.

Super-Selective Intraarterial Cerebral Infusion of Cetuximab (Erbitux) for Treatment of Relapsed/Refractory GBM and AA

Phase I Trial of Super-Selective Intraarterial Cerebral Infusion of Cetuximab (Erbitux) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma

Northwell Health

Director of Neurosurgery

Disease Attributes

Gamma-retroviral MSGV1 139 scFv EGFRvIII CAR gene-modified T cells

EGFRvIII-CARs

Daniel Landi, MD

David Ashley, MBBS, FRACP, PhD

The goal of this protocol is to transfer autologous peripheral blood mononuclear cells (PBMCs) transduced with genes encoding a chimeric antigen receptor (CAR) that recognizes epidermal growth factor receptor variant III (EGFRvIII) tumor-specific antigen into patients with recurrent glioblastoma (GBM) following stereotactic radiosurgery (SRS). The CAR used is targeted to a tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, which is expressed on a subset of patients. Normal PBMCs derived from patients with GBM are genetically engineered with a viral vector encoding the CAR and infused directly into the patient's tumor with the aim of mediating regression of their tumors. Despite our CAR being targeted to a tumor specific antigen, given the prior toxicity using CARs that were not targeted to tumor-specific antigens, the investigators elected to begin with very low doses of cells. Enrollment on this study was suspended in April 2020 while an amendment to reduce the anticipated number of participants was under review and approved. The decision to terminate the study was made in January, 2021 to shift toward the next iteration of a related CAR T cell trial.

Patients with evidence of radiographic recurrence who expressed EGFRvIII on their original tumor diagnosis had autologous PBMCs harvested by leukapheresis. These autologous PBMCs were transduced with a retrovirus containing the sequences for the EGFRvIII CAR and sent to the Duke Radiopharmacy for radiolabeling with 111Indium (111In). Within 2-3 weeks of leukapheresis, on Day -4 to -2, patients had a BrainLab MRI to prepare for biopsy and catheter placement. On Day -1, the patient underwent standard of care (SOC) stereotactic biopsy under local anesthesia to confirm tumor recurrence. At the time of biopsy, prior to catheter insertion and administration of study drug, the presence of recurrent tumor was confirmed by histopathology. If tumor recurrence was confirmed, a catheter was placed intratumorally for delivery of EGFRvIII-CARs by Convection Enhanced Delivery (CED).

SRS will took place on Day 0 (+1 day) and 111In-labeled EGFRvIII-CARs were infused on the same day over a 6 to 6.5 hour period immediately after SRS.

On days 1 and 2 after 111In-labeled EGFRvIII-CAR infusion, whole planar imaging followed by Single-Photon Emission Computed Tomography (SPECT) Computed Tomography (CT) imaging assessed the intracerebral and systemic localization of the 111In-labeled EGFRvIII-CARs that described the distribution of EGFRvIII-CARs within the brain and systemically.

This protocol was designed to determine the maximum tolerated dose (MTD) of a novel, tumor-specific treatment with autologous EGFRvIII-CARs. The proposed starting dose was 2.5 x 10\^8 of 111In-labeled cells in 3 milliliters (mL). The infusion flow rate was fixed at 0.5 mL/hr.

Enrollment on this study was suspended in April 2020 while an amendment to reduce the anticipated number of participants was under review and approved. Upon approval of this amendment, the enrollment suspension remained due to a change in access to necessary equipment for CAR manufacturing. The decision to terminate the study was made in January, 2021 to shift toward the next iteration of a related CAR T cell trial. The knowledge gained from this study experience is directing our next CAR T-cell platform and will be used to secure additional funding.

Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM

INTERCEPT: INTracerebral EGFR-vIII Chimeric Antigen Receptor Gene-Modified T CElls for PaTients With Recurrent GBM

MTD of EGFRvIII-CAR gene-modified T cells when administered intracerebrally by CED after SRS in patients with recurrent GBM

Change in volume of distribution and maximal percentage of enhanced tumor volume covered

Change in the volume of distribution of 111In-labeled EGFRvIII-CARs present in each body area (neck, chest, abdomen, pelvis, and extremities)

The time between SRS / CAR treatment and death or last follow-up

The time between SRS / CAR treatment and first failure (death or disease progression)

National Cancer Institute (NCI)

Duke Cancer Institute

Gary Archer Ph.D.

Assistant Professor of Neurosurgery

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Diuretics

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

Intra-arterial Cetuximab

Intra-arterial Mannitol

Tamika Wong, MPH

David Langer, MD

Rafael Ortiz, MD

Jed Pollack, MD

Anuj Goenka, MD

Christopher Filippi, MD

Sherese Fralin, NP

Ashley Ray, NP

Karissa Tan, NP

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

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 RANO 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

Principal Investigator

Bevacizumab

Antibodies, Monoclonal

Angiogenesis Inhibitors

Endothelial Growth Factors

Growth Inhibitors

About half of the patients who have never received treatment with bevacizumab will receive rindopepimut/GM-CSF in a blinded fashion in combination with bevacizumab.

About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.

Patients with progressive disease while currently on or within two months after discontinuing bevacizumab will be administered rindopepimut/GM-CSF while continuing (or restarting if they had stopped bevacizumab).

A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.

Rindopepimut/GM-CSF will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM-CSF.

KLH will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 100 mcg of KLH.

The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used drug bevacizumab can improve progression free survival (slowing the growth of tumors) of patients with relapsed EGFRvIII positive glioblastoma.

This Phase II study will enroll patients into three groups. Group 1 are patients who have never been treated with bevacizumab. These patients will be randomly assigned to receive either rindopepimut/GM-CSF or KLH, each along with bevacizumab. Treatment assignment for Group 1 will be blinded. Group 2 and Group 2C patients are those who are refractory to bevacizumab (experienced recurrence or progression of glioblastoma while on bevacizumab or within 2 months of discontinuing bevacizumab). These patients will all receive rindopepimut/GM-CSF along with bevacizumab. Patients will be treated until disease progression or intolerance and all patients will be followed for survival. Patients may be treated with other therapies that are not part of the study after discontinuing treatment with the study vaccine.

A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma

A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma

Evaluate the antitumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the progression-free survival rate at 6 months post-Day 1 (PFS 6).

Evaluate the anti-tumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the objective response rate (ORR) for patients with measurable disease at study entry.

Safety and tolerability will be evaluated by comparing the treatment regimens in regards to vital sign measurements, physical and neurological examinations, adverse events reporting, and Karnofsky performance status

Evaluated by comparing the treatment regimens for anti-tumor activity, including objective response rate, overall progression free survival (PFS), and overall survival (OS) for Groups 1 and 2; and PFS6, overall PFS, and OS for Group 2C.

Characterize the EGFRvIII specific immune response to rindopepimut.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma	NCT01480479	Glioblastoma Small Cell Glio... Giant Cell Glio... Gliosarcoma Glioblastoma Wi...	Rindopepimut (C... Temozolomide KLH	18 Years -	Celldex Therapeutics
AMG 595 First-in-Human in Recurrent Gliomas	NCT01475006	Advanced Malign... Anaplastic Astr... Glioblastoma Mu...	AMG 595	18 Years -	Amgen
Super-Selective Intraarterial Cerebral Infusion of Cetuximab (Erbitux) for Treatment of Relapsed/Refractory GBM and AA	NCT01238237	Glioblastoma Mu... ANAPLASTIC ASTR... GBM Anaplastic Astr...	Superselective ...	18 Years -	Northwell Health
AMG 595 First-in-Human in Recurrent Gliomas	NCT01475006	Advanced Malign... Anaplastic Astr... Glioblastoma Mu...	AMG 595	18 Years -	Amgen
Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM	NCT03283631	Recurrent Gliob... Recurrent Glios...	EGFRvIII-CARs	18 Years -	Duke University
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
A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma	NCT01498328	Glioblastoma Small Cell Glio... Giant Cell Glio... Gliosarcoma Glioblastoma Wi... Recurrent Gliob... Relapsed Gliobl...	Bevacizumab Rindopepimut (C... KLH	18 Years -	Celldex Therapeutics
A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma	NCT01498328	Glioblastoma Small Cell Glio... Giant Cell Glio... Gliosarcoma Glioblastoma Wi... Recurrent Gliob... Relapsed Gliobl...	Bevacizumab Rindopepimut (C... KLH	18 Years -	Celldex Therapeutics

Spots Global Cancer Trial Database for egfrviii

Every month we try and update this database with for egfrviii cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for egfrviii

Every month we try and update this database with for egfrviii cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for egfrviii cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.