Omental Tissue Autograft in Human Recurrent Glioblastoma Multiforme (rGBM)

Study Overview
=================
Brief Summary
-----------------
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.

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).

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

Conditions
-----------------
Glioma, Glioma, Malignant, Glioblastoma, Glioblastoma Multiforme, Glioblastoma Multiforme of Brain, GBM, Brain Cancer, High Grade Glioma

Intervention / Treatment
-----------------
* Procedure: Laparoscopically harvested omental tissue autograft


Participation Criteria
=================
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. Able to understand and willing to sign an institutional review board (IRB)- approved written informed consent document Inclusion criteria considered during surgery: Subject has a histologically confirmed (frozen section) diagnosis of recurrent WHO Grade IV glioblastoma multiforme (GBM). Omental graft is technically feasible. Exclusion Criteria: Subject, if female, is pregnant or is breast feeding. 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. Subject has had prior abdominal surgery. Subject has severe renal insufficiency rendering gadolinium MRI contraindicated. Subject who are unable to have an MRI scan for any reason.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laparoscopically harvested omental tissue autograft<br>Use of laparoscopically harvested omental autografts into the resection cavity of recurrent glioblastoma multiforme (rGBM) patients. | Procedure: Laparoscopically harvested omental tissue autograft<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
blood brain barrier, omentum autograft, omental autograft, omentum, omental