Neoplasms

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Glioblastoma

Glioma

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Neoplasms, Neuroepithelial

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Neuroectodermal Tumors, Primitive

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Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

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Bevacizumab

Temozolomide

Antineoplastic Agents, Immunological

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Alkylating Agents

Repeated Superselective Intraarterial Cerebral infusion (SIACI) of Bevacizumab (Avastin) with Temozolomide and Radiation

Standard of care Temozolomide and Radiation

Subjects who are assigned to the IA BV+TMZ/RT group (Treatment Group), in addition to your standard of care cancer treatment, you will have a dose of bevacizumab delivered directly to your brain through superselective intra-cranial intra-arterial catheterization of the arteries that supply blood to your brain tumor along with the start of the initial 42 day oral temozolomide treatment. IA BV will be repeated every three months for a total of 3 infusions.

Subjects who are assigned to the TMZ/RT alone group (Control Group) you will receive standard of care cancer treatment that involves a daily oral dose of temozolomide for 42 days with radiation to the tumor followed by 28 days of rest and then repeated maintenance treatment cycles of daily oral temozolomide 5 days on and 23 days off.

Temozolomide and Radiation Alone

John Boockvar, MD

Tamika Wong, MPH

David Langer, MD

Rafael Ortiz, MD

Olivia Albers, NP

Amy McKewon, NP

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.

The investigators have completed a Phase I clinical trial that has shown that Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (BV) is safe up to a dose of 15mg/kg in patients with recurrent malignant glioma. Additionally, the investigators have shown in a recently completed Phase I/II clinical trial, that SIACI BV improves the median progression free survival (PFS) from 4-6 months to 11.5 months and overall survival (OS) from 12-15 months to 23 months in patients with newly diagnosed GBM. Therefore, this two-arm, randomized trial (2:1) is a follow up study to these trials and will ask simple questions: Will this repeated SIACI treatment regimen increase progression free survival (PFS-primary endpoint) and overall survival (OS-secondary endpoint) when compared with standard of care in patients with newly diagnosed GBM? Exploratory endpoints will include adverse events and safety analysis as well as quality of life (QOL) assessments. The investigators expect that this project will provide important information regarding the utility of repeated SIACI BV therapy for newly diagnosed GBM and may alter the way these drugs are delivered to our patients in the near future.

Those randomized to the treatment group (IA BV+TMZ/RT )the experimental aspects will include:

1. Subjects will first be treated with Mannitol prior to IA BV infusion. Mannitol is delivered IA, 12.5 mL over 2 minutes in order to disrupt the blood brain barrier. IA mannitol has been used in several thousand patients in previous studies for the IA delivery of chemotherapy for malignant glioma.
2. Subjects will then be treated with repeated IA BV. Each patient will receive one dose of IA BV on day 30, followed by chemoradiation. IA BV will be repeated every three months for a total of 3 infusions.

Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed GBM

A Phase III Randomized Trial of Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (Avastin) With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed Glioblastoma (GBM)

The primary end point will be overall survival (OS). Overall survival is defined as the time from randomization until death due to any cause. Participants who are still alive at the time of analysis will be censored at their last known alive date.

The secondary end point will be progression-free survival (PFS). PFS is defined from the time of randomization until first documentation of disease progression (according to RANO Criteria), or death from any cause, whichever occurs first. Participants without documented disease progression at the time of analysis will be censored at the time of their last tumor assessment.

Northwell Health

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed GBM	NCT05271240	Glioblastoma Glioblastoma Mu... Glioma, Maligna... GBM Brain Cancer Glioblastoma, I... Glioblastoma Mu...	Repeated Supers... Temozolomide an...	18 Years -	Northwell Health
Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed GBM	NCT05271240	Glioblastoma Glioblastoma Mu... Glioma, Maligna... GBM Brain Cancer Glioblastoma, I... Glioblastoma Mu...	Repeated Supers... Temozolomide an...	18 Years -	Northwell Health
Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed GBM	NCT05271240	Glioblastoma Glioblastoma Mu... Glioma, Maligna... GBM Brain Cancer Glioblastoma, I... Glioblastoma Mu...	Repeated Supers... Temozolomide an...	18 Years -	Northwell Health

Spots Global Cancer Trial Database for repeated superselective intraarterial cerebral infusion (siaci) of bevacizumab (avastin) with temozolomide and radiation