Omental Tissue Autograft in Human Recurrent Glioblastoma Multiforme (rGBM)

Laparoscopically Harvested Omental Tissue Autograft to Bypass the Blood Brain Barrier (BBB) in Human Recurrent Glioblastoma Multiforme (rGBM)

This single center, single arm, open-label, phase I study will assess the safety of laparoscopically harvested autologous omentum, implanted into the resection cavity of recurrent glioblastoma multiforme (GBM) patients.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Glioblastoma; Brain Cancer; Glioblastoma Multiforme; High Grade Glioma; GBM; Glioma, Malignant; Glioblastoma Multiforme of Brain
• Intervention / Treatment: Procedure: Laparoscopically harvested omental tissue autograft

Detailed Description

Laparoscopically harvested omental grafts are commonly used to fill surgical cavities after resection of head and neck cancers. Investigators hypothesize that an omental tissue graft implanted into our patients with resected recurrent GBM may be used as a readily available and accessible means of circumventing the blood brain barrier (BBB) selectively and focally. The laparoscopically harvested omental graft omentum would easily conform to many resected GBM cavities in our human patients with acceptable risk. The predictable and rich vascular anatomy of a laparoscopically harvested piece of omentum makes it an ideal tissue for cases of previously irradiated and/or infected wound beds. This is why it is successfully used in head and neck and skull base tumors. The permeability of the new blood vessels formed between the omental graft and the cortical brain surface should allow for improved delivery of chemotherapeutics 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 tumor (BAT). Milky spots within the greater omentum are very small white-coloured areas of lymphoid tissue will also provide direct deposition of immune cells such as dendritic, macrophages and lymphocytes into the milieu of the resected GBM. The milky spots are made up of mesenchymal cells and are covered in a layer of mesothelium. These structures surround the small blood vessels. The enclosing mesothelium contains macrophages, lymphocytes and mast cells. They are also known as secondary lymphoid organs. Most milky spots contain extremely thin-walled lymphatic capillaries. In addition, the technique of fat grafting has been reliably used since 1990 as a way to improve and enhance wound healing, scar healing, as well as tissue augmentation and tissue repair following radiation injury.

All subjects included in the study will undergo standard surgical resection for diagnosed recurrent GBM. Following the resection, the surgical cavity will be lined with a laparoscopically harvested piece of autologous omentum. The patient's dura, bone and scalp will be closed as is customary. The subject will be followed for side effects within 72 hours, 7 days, 30 days, 60 days, 120 days and 180 days. Risk assessment will include seizure, stroke, infection, tumor progression, and death.

The investigators aim to prove that this commonly surgical technique for head and neck cancers and reconstructive surgery is safe in a small human cohort of patients with resected recurrent GBM and may improve progression-free survival (PFS) and overall survival (OS).

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tamika Wong, MPH; Phone Number: 212-434-4836; Email: twong4@northwell.edu
• Study Contact Backup: Name: John Boockvar, MD; Phone Number: 212-434-3900; Email: jboockvar@northwell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10075
      • Recruiting
      • Lenox Hill Brain Tumor Center
      • Contact: Tamika Wong, MPH; Phone Number: 212-434-4836; Email: twong4@northwell.edu
      • Contact: John Boockvar, MD; Phone Number: 212-434-3900; Email: jboockvar@northwell.edu
      • Sub-Investigator: David Langer, MD
      • Sub-Investigator: Tamika Wong, MPH
      • Sub-Investigator: Olivia Albers, NP
      • Principal Investigator: John Boockvar, MD
      • Sub-Investigator: Netanel Ben-Shalom, MD
      • Sub-Investigator: Avraham Zlochower, MD
      • Sub-Investigator: Robert A Andrews, MD
      • Sub-Investigator: Vadim Zhigin, PA-C
      • Sub-Investigator: Amy McKeown, NP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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. Able to understand and willing to sign an institutional review board (IRB)- approved written informed consent document

Inclusion criteria considered during surgery:

1. Subject has a histologically confirmed (frozen section) diagnosis of recurrent WHO Grade IV glioblastoma multiforme (GBM).
2. Omental graft is technically feasible.

Exclusion Criteria:

1. Subject, if female, is pregnant or is breast feeding.
2. Subject intends to participate in another clinical trial.
3. Subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery.
4. Subject has an active infection requiring treatment.
5. Subject has radiographic evidence of multi-focal disease or leptomeningeal dissemination.
6. 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
7. Subject has a known positive test for human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection.
8. 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.
9. Subject has had prior abdominal surgery.
10. Subject has severe renal insufficiency rendering gadolinium MRI contraindicated.
11. Subject who are unable to have an MRI scan for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laparoscopically harvested omental tissue autograft; Use of laparoscopically harvested omental autografts into the resection cavity of recurrent glioblastoma multiforme (rGBM) patients.	Procedure: Laparoscopically harvested omental tissue autograft; Standard neurosurgical removal of recurrent GBM,; removal of fat from abdomen called omentum using a thin tube with a camera (laparoscopically),; the omental fat will be transferred and implanted into brain tumor cavity,; standard closure of surgical resection cavity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety parameter: proportion of patients experiencing rapidly progressive disease as indicated by MRI using RANO Criteria harvested omental graft for recurrent glioblastoma multiforme (rGBM).	Increase in tumor size relative to baseline will be measured using RANO and assessed by MRI throughout study at within 72 hours, 7 days, 30 days, 60 days, 120 days and 180 days. Rapidly progressive disease is defined as 25% growth relative to baseline.	Study Day 1 - Day 180
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 within 72 hours, 7 days, 30 days, 60 days, 120 days and 180 days.	Study Day 1 - Day 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	The proportion of patients who are alive at 6 months from omental implantation and are progression-free will be estimated using standard methods for proportions, along with the associated exact 95% confidence interval.	6 months
Overall Survival (OS)	OS will be calculated as the time from treatment initiation (omental autograft) to the time of death.	6 months
Percent of screen fails	To tabulate the number and % of screen failures and understand the reason for screen failures (omental autograft not viable etc.) will be tabulated and summarized.	Study Day 1 - 24 Months

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: John Boockvar, MD, Northwell Health

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: blood brain barrier; omentum; omentum autograft; omental autograft; omental
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Glioblastoma; Glioma; Brain Neoplasms
• Other Study ID Numbers: 22-0994

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No