Back to resultsSurgical Tissue Flap to Bypass the Blood Brain Barrier in GBM
Primary Purpose
Glioblastoma, Glioblastoma Multiforme, GBM
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap to bypass the blood brain barrier (BBB)
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring tissue autograft, blood brain barrier
Eligibility Criteria
Inclusion Criteria:
- Subject is a male or female 18 years of age or older.
- Subject is undergoing planned resection of known or suspected GBM.
- Subject has a Karnofsky Performance Status (KPS) 70% or greater.
- Subject has a life expectancy of at least 6 months, in the opinion of the Investigator.
- Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ≥ 80% resection of enhancing region.
- Subject must be able to undergo MRI evaluation.
Subject meets the following laboratory criteria:
- White blood count ≥ 3,000/µL
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin > 10.0 g/dL (transfusion and/or ESA allowed)
- Total bilirubin and alkaline phosphatase ≤ 2x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN
- Blood urea nitrogen (BUN) and creatinine < 1.5 x ULN
- Females of reproductive potential must have a negative serum pregnancy test and be willing to use an acceptable method of birth control.
- Males of reproductive potential must be willing to use an acceptable method of birth control to ensure effective contraception with partner.
- Able to understand and willing to sign an institutional review board (IRB)-approved written informed consent document (legally authorized representative permitted).
Inclusion criteria considered during surgery:
- Subject has a histologically confirmed (frozen section) diagnosis of WHO Grade IV glioblastoma multiforme (GBM).
- TPFF and/or pericranial flap is technically feasible.
Exclusion Criteria:
- Subject, if female, is pregnant or is breast feeding.
- Subject has initiated chemotherapy or radiation treatment for diagnosis of or GBM.
- Subject intends to participate in another clinical trial.
- Subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery.
- Subject has an active infection requiring treatment.
- Subject has radiographic evidence of multi-focal disease or leptomeningeal dissemination.
- Subject has a history of other malignancy, unless the patient has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment.
- Subject has a known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection.
- Subject has a history or evidence of any other clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
Sites / Locations
- Lenox Hill Brain Tumor Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Surgical tissue autograft: TPF flap/pericranial flap
Arm Description
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
Outcomes
Primary Outcome Measures
Safety parameter: proportion of patients experiencing rapidly progressive disease as indicated by MRI using RANO Criteria
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
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.
Secondary Outcome Measures
Progression Free Survival (PFS)
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03630289
Brief Title
Surgical Tissue Flap to Bypass the Blood Brain Barrier in GBM
Official Title
Tissue Autograft to Bypass the Blood Brain Barrier (BBB) in Human Glioblastoma Multiforme (GBM)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 27, 2018 (Actual)
Primary Completion Date
May 15, 2023 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwell Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
Detailed Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Glioblastoma Multiforme, GBM, Brain Cancer
Keywords
tissue autograft, blood brain barrier
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Surgical tissue autograft: TPF flap/pericranial flap
Arm Type
Experimental
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
Tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap to bypass the blood brain barrier (BBB)
Other Intervention Name(s)
surgical tissue flap, tissue autograft
Intervention Description
Surgical tissue autograft of pedicled temporoparietal fascial (TPF) or pericranial flap into the resection cavity of newly diagnosed glioblastoma multiforme (GBM) patients.
Primary Outcome Measure Information:
Title
Safety parameter: proportion of patients experiencing rapidly progressive disease as indicated by MRI using RANO Criteria
Description
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.
Time Frame
Study Day 1-180
Title
Safety parameter: proportion of patients experiencing increase in seizures, stroke, and infection
Description
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.
Time Frame
Study Day 1-180
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
6 months
Title
Overall Survival (OS)
Description
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.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subject is a male or female 18 years of age or older.
Subject is undergoing planned resection of known or suspected GBM.
Subject has a Karnofsky Performance Status (KPS) 70% or greater.
Subject has a life expectancy of at least 6 months, in the opinion of the Investigator.
Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ≥ 80% resection of enhancing region.
Subject must be able to undergo MRI evaluation.
Subject meets the following laboratory criteria:
White blood count ≥ 3,000/µL
Absolute neutrophil count ≥ 1,500/µL
Platelets ≥ 100,000/µL
Hemoglobin > 10.0 g/dL (transfusion and/or ESA allowed)
Total bilirubin and alkaline phosphatase ≤ 2x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN
Blood urea nitrogen (BUN) and creatinine < 1.5 x ULN
Females of reproductive potential must have a negative serum pregnancy test and be willing to use an acceptable method of birth control.
Males of reproductive potential must be willing to use an acceptable method of birth control to ensure effective contraception with partner.
Able to understand and willing to sign an institutional review board (IRB)-approved written informed consent document (legally authorized representative permitted).
Inclusion criteria considered during surgery:
Subject has a histologically confirmed (frozen section) diagnosis of WHO Grade IV glioblastoma multiforme (GBM).
TPFF and/or pericranial flap is technically feasible.
Exclusion Criteria:
Subject, if female, is pregnant or is breast feeding.
Subject has initiated chemotherapy or radiation treatment for diagnosis of or GBM.
Subject intends to participate in another clinical trial.
Subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery.
Subject has an active infection requiring treatment.
Subject has radiographic evidence of multi-focal disease or leptomeningeal dissemination.
Subject has a history of other malignancy, unless the patient has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment.
Subject has a known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection.
Subject has a history or evidence of any other clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Boockvar, MD
Organizational Affiliation
Northwell Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lenox Hill Brain Tumor Center
City
New York
State/Province
New York
ZIP/Postal Code
10075
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Surgical Tissue Flap to Bypass the Blood Brain Barrier in GBM
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