Surgical Tissue Flap to Bypass the Blood Brain Barrier in Glioblastoma

• ClinicalTrials.gov Identifier: NCT05954858
• Recruitment Status: Recruiting
• First Posted: July 20, 2023
• Last Update Posted: August 3, 2023
• Sponsor: Northwell Health
• Information provided by (Responsible Party): John Boockvar, MD Zucker SOM @Hofstra/Northwell, Northwell Health

Tracking Information

• First Submitted Date: July 13, 2023
• First Posted Date: July 20, 2023
• Last Update Posted Date: August 3, 2023
• Actual Study Start Date: June 29, 2023
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 13, 2023)

Progression Free Survival (PFS) [ Time Frame: 6 months ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 13, 2023)

Overall Survival (OS) [ Time Frame: 2 years ]

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Surgical Tissue Flap to Bypass the Blood Brain Barrier in Glioblastoma
• Official Title: Tissue Autograft to Bypass the Blood Brain Barrier (BBB) in Human Glioblastoma Multiforme (GBM)

Brief Summary

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).

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. 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Glioma, Malignant
• Glioblastoma
• Glioblastoma Multiforme
• Glioblastoma Multiforme, Adult
• High Grade Glioma
• GBM
• Brain Cancer

Intervention

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.

Other Names:

• surgical tissue flap
• tissue autograft

Study Arms

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

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 13, 2023): 32
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2026
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Subject is a male or female 18 years of age or older.
2. Subject is undergoing planned resection of known or suspected GBM.
3. Subject has a Karnofsky Performance Status (KPS) 70% or greater.
4. Subject has a life expectancy of at least 6 months, in the opinion of the Investigator.
5. Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ≥ 80% resection of enhancing region.
6. Subject must be able to undergo MRI evaluation.

7. Subject meets the following laboratory criteria:

   1. White blood count ≥ 3,000/μL
   2. Absolute neutrophil count ≥ 1,500/μL
   3. Platelets ≥ 100,000/μL
   4. Hemoglobin > 10.0 g/dL (transfusion and/or ESA allowed)
   5. Total bilirubin and alkaline phosphatase ≤ 2x institutional upper limit of normal (ULN)
   6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN
   7. Blood urea nitrogen (BUN) and creatinine < 1.5 x ULN
8. Females of reproductive potential must have a negative serum pregnancy test and be willing to use an acceptable method of birth control.
9. Males of reproductive potential must be willing to use an acceptable method of birth control to ensure effective contraception with partner.
10. 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:

1. Subject has a histologically confirmed (frozen section) diagnosis of WHO Grade IV glioblastoma multiforme (GBM).
2. TPFF and/or pericranial flap is technically feasible.

Exclusion Criteria:

1. Subject, if female, is pregnant or is breast feeding.
2. Subject has initiated chemotherapy or radiation treatment for diagnosis of or GBM.
3. Subject intends to participate in another clinical trial
4. Subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery.
5. Subject has an active infection requiring treatment.
6. Subject has radiographic evidence of multi-focal disease or leptomeningeal dissemination.
7. 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
8. Subject has a known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection.
9. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: John Boockvar, MD; 212-434-3900; jboockvar@northwell.edu

Contact: Tamika Wong, MPH; 212-434-4836; twong4@northwell.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05954858
• Other Study ID Numbers: 23-0385
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: John Boockvar, MD Zucker SOM @Hofstra/Northwell, Northwell Health
• Original Responsible Party: Same as current
• Current Study Sponsor: Northwell Health
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: John Boockvar, MD; Feinstein Institute for Medical Research/Lenox Hill Hospital

• PRS Account: Northwell Health
• Verification Date: August 2023