Surgical Tissue Flap to Bypass the Blood Brain Barrier in GBM
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03630289|
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : November 19, 2019
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).
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Glioblastoma Multiforme GBM Brain Cancer||Procedure: Tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap to bypass the blood brain barrier (BBB)||Not Applicable|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Tissue Autograft to Bypass the Blood Brain Barrier (BBB) in Human Glioblastoma Multiforme (GBM)|
|Actual Study Start Date :||July 27, 2018|
|Estimated Primary Completion Date :||July 27, 2020|
|Estimated Study Completion Date :||July 27, 2020|
Experimental: Surgical tissue autograft: TPF flap/pericranial flap
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
Procedure: Tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap to bypass the blood brain barrier (BBB)
Surgical tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap into the resection cavity of newly diagnosed glioblastoma multiforme (GBM) patients.
- Safety parameter: proportion of patients experiencing rapidly progressive disease as indicated by MRI using RANO Criteria [ Time Frame: Study Day 1-180 ]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.
- Safety parameter: proportion of patients experiencing increase in seizures, stroke, and infection [ Time Frame: Study Day 1-180 ]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.
- Progression Free Survival (PFS) [ Time Frame: 6 months ]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.
- Overall Survival (OS) [ Time Frame: 2 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03630289
|Contact: John Boockvar, MDfirstname.lastname@example.org|
|Contact: Tamika Wong, MPHemail@example.com|
|United States, New York|
|Lenox Hill Brain Tumor Center||Recruiting|
|New York, New York, United States, 10075|
|Contact: John Boockvar, MD 212-434-3900 firstname.lastname@example.org|
|Contact: Tamika Wong, MPH 212-434-4836 email@example.com|
|Principal Investigator: John Boockvar, MD|
|Sub-Investigator: David Langer, MD|
|Sub-Investigator: Peter Constantino, MD|
|Sub-Investigator: Sherese Fralin, NP|
|Sub-Investigator: Ashley Ray, NP|
|Sub-Investigator: Christopher Filippi, MD|
|Sub-Investigator: Tamika Wong, MPH|
|Sub-Investigator: Lukas Faltings|
|Sub-Investigator: Mona Li|
|Principal Investigator:||John Boockvar, MD||Northwell Health|