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Use of a pedicled autologous piece of tissue called the temporoparietal fascial (TPF) flap or pericranial flap into the resection cavity of newly diagnosed glioblastoma multiforme (GBM) patients

Surgical tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap into the resection cavity of newly diagnosed glioblastoma multiforme (GBM) patients.

Tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap to bypass the blood brain barrier (BBB)

John Boockvar, MD

Tamika Wong, MPH

David Langer, MD

Netanel Ben-Shalom, MD

Randy D'Amico, MD

Deborah Gruber, MD

Avraham Zlochower, MD

Vadim Zhigin, PA

Olivia Albers, NP

Amy McKewon, NP

This single center, single arm, open-label, phase 2 study will assess the safety and efficacy of a pedicled temporoparietal fascial (TPF) or pericranial flap into the resection cavity of newly diagnosed glioblastoma multifome (GBM) patients.

The objective of the Phase 2 study is to demonstrate that this surgical technique is safe and effective in a human cohort of patients with resected newly diagnosed AA or GBM and may improve progression-free survival (PFS) and overall survival (OS).

Glioblastoma (GBM) is the most common primary central nervous system malignancy in adults, and accounts for over half of all malignant brain tumors. The prognosis for newly diagnosed GBM is extremely poor even with Stupp protocol consisting of surgery followed by temozolomide and radiotherapy. For newly diagnosed GBM the median overall survival (OS) is only 15 months, and the median progression-free survival (PFS) is a mere 5-6 months with only 53.9% of patients having 6 month PFS.

This Phase 2 study is an extension of our recently completely enrolled Phase I trial which showed the initial safety of a TPF into the resection cavity of newly diagnosed GBM. All 36 subjects included in this Phase 2 study will initially undergo standard surgical resection for newly diagnosed GBM. Following the resection, the surgical cavity will be lined with a long pedicled, autologous piece of tissue called a temporoparietal fascial flap or pericranium. The patient's dura, bone and scalp will be closed as is customary. The subject will be followed for side effects at 72 hours, 7 days, 30 days, 60 days, 120 days and 180 days. The primary outcome measure will be progression free survival (PFS) and secondary outcome measures will include overall survival (OS). Risk assessment will include seizure, stroke, infection, tumor progression, and death.

Surgical Tissue Flap to Bypass the Blood Brain Barrier in Glioblastoma

Tissue Autograft to Bypass the Blood Brain Barrier (BBB) in Human Glioblastoma Multiforme (GBM)

PFS is defined as time from surgery until first known disease progression or death from any cause, whichever occurs first.

OS will be calculated as the time from treatment initiation (TPF implantation) to the time of death.

Northwell Health

Principal Investigator

This study assesses the safety of using tissue autograft of a pedicled temporoparietal fascial (TPF) or pericranial flap into the resection cavity of newly diagnosed glioblastoma multiforme (GBM) patients.

The objective of the study is to demonstrate that this surgical technique is safe in a small human cohort of patients with resected newly diagnosed GBM and may improve progression-free survival (PFS).

Glioblastoma (GBM) is the most common primary central nervous system malignancy in adults, and accounts for over half of all malignant brain tumors. The prognosis for newly diagnosed GBM is extremely poor even with Stupp protocol consisting of surgery followed by temozolomide and radiotherapy. Present therapies are inadequate, as evidenced by the low 5-year survival rate for brain cancer patients, with median survival at approximately 12 months and treatment for GBM remains a significant unmet clinical need in oncology.

All subjects included in the study will initially undergo standard surgical resection for newly diagnosed GBM. Following the resection, the surgical cavity will be lined with a long pedicled, autologous piece of tissue called a temporoparietal fascial flap or pericranium. The patient's dura, bone and scalp will be closed as is customary. The permeability of the blood vessels of the TPF or pericranial flap should allow for improved delivery of therapeutics and immune cells (macrophages and T cells) into the vicinity, extracellular space and microenvironment of the resected tumor cavity including the brain adjacent to the GBM. The TPF or pericranial flap would easily conform to many resected GBM cavities in our human patients with acceptable risk. The TPF and pericranial flap with its predictable and rich vascular anatomy have been shown to be an ideal flap for cases of previously irradiated and/or infected wound beds.

The investigators hypothesize that a TPF or pericranial flap that is harvested in our patients with resected GBM may be used as a readily available and accessible means of circumventing the blood brain barrier selectively and focally. The investigators aim to prove that this surgical technique is safe in a small human cohort of patients with resected newly diagnosed GBM and may improve progression-free survival (PFS).

Surgical Tissue Flap to Bypass the Blood Brain Barrier in GBM

Increase in tumor size relative to baseline will be measured using RANO and assessed by MRI throughout study at 24 hours, 7 days, 30 days, 60 days, 90 days, 180 days. Rapidly progressive disease is defined as 25% growth relative to baseline.

Increase in seizures (defined as 15% relative to baseline), occurrence of a stroke, or occurrence of a severe infection will be determined throughout study at 24 hours, 7 days, 30 days, 60 days, 90 days, 180 days.

The proportion of patients who are alive at 6 months from flap implantation and are progression-free will be estimated using standard methods for proportions, along with the associated exact 95% confidence interval. All patients will be followed for a minimum of six months from the time of implantation. For this analysis, patients who are lost to follow-up prior to 6 months will be (conservatively) assumed as treatment failures at 6 months. The investigators will also estimate PFS using the Kaplan-Meier Product Limit Method. For this analysis, subjects who are alive and have not progressed as of the date of last follow-up will be considered censored.

OS will be calculated as the time from treatment initiation (TPF implantation) to the time of death. Subjects who are alive as of the date of last follow-up will be considered censored for survival. OS will be analyzed using the Kaplan-Meier Product Limit Method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Surgical Tissue Flap to Bypass the Blood Brain Barrier in Glioblastoma	NCT05954858	Glioma, Maligna... Glioblastoma Glioblastoma Mu... Glioblastoma Mu... High Grade Glio... GBM Brain Cancer	Tissue autograf...	18 Years -	Northwell Health
Surgical Tissue Flap to Bypass the Blood Brain Barrier in GBM	NCT03630289	Glioblastoma Glioblastoma Mu... GBM Brain Cancer	Tissue autograf...	18 Years -	Northwell Health
Surgical Tissue Flap to Bypass the Blood Brain Barrier in Glioblastoma	NCT05954858	Glioma, Maligna... Glioblastoma Glioblastoma Mu... Glioblastoma Mu... High Grade Glio... GBM Brain Cancer	Tissue autograf...	18 Years -	Northwell Health
Surgical Tissue Flap to Bypass the Blood Brain Barrier in GBM	NCT03630289	Glioblastoma Glioblastoma Mu... GBM Brain Cancer	Tissue autograf...	18 Years -	Northwell Health

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