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

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04222309
• Other study ID #: 19-0801
• Status: Suspended
• Phase: Phase 1
• Start date: January 6, 2020
• Est. completion date: January 31, 2025

Study information

• Verified date: August 2023
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This single center, single arm, open-label, phase I study will assess the safety of a laparoscopically harvested omental free flap into the resection cavity of recurrent glioblastoma multiforme (GBM) patients. All participants 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 omental free flap. The participant's dura, bone and scalp will be closed as is customary. The participant will be followed for side effects within 72 hours, 7 days, 30 days, 90 days and 180 days. Risk assessment will include seizure, stroke, infection, tumor progression, and death.

Description:

Laparoscopically harvested omental free flaps are commonly used to fill surgical cavities after resection of head and neck cancers. The investigators hypothesize that a laparoscopically harvested omental free flap in 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 free flap with its long vascular pedicle length, wide rotational arc and available surface area 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 omental free makes it an ideal flap 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 blood vessels of the laparoscopically harvested omental free flap 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 omentum will also provide direct deposition of immune cells such as dendritic, macrophages and lymphocytes into the milieu of the resected GBM. The investigators aim to prove that this commonly surgical technique for head and neck cancers is safe in a small human cohort of patients with resected recurrent GBM and may improve progression-free survival (PFS).

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 10
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 free flap 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.

Related Conditions & MeSH terms

• Brain Cancer
• Brain Neoplasms
• GBM
• Glioblastoma
• Glioblastoma Multiforme
• Glioblastoma Multiforme of Brain
• Glioma
• Glioma, Malignant

Intervention

Procedure:
• Laparoscopically harvested omental free flap
Laparoscopically harvested omental free flap into the resection cavity of recurrent glioblastoma multiforme (GBM) patients.

Locations

Country	Name	City	State
United States	Lenox Hill Brain Tumor Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 within 72 hours, 7 days, 30 days, 90 days and 180 days. Rapidly progressive disease is defined as 25% growth relative to baseline.	Study Day 1-180
Primary	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, 90 days and 180 days.	Time Frame: Study Day 1-180
Secondary	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.	6 months
Secondary	Overall Survival (OS)	OS will be calculated as the time from treatment initiation (flap implantation) to the time of death.	6 months
Secondary	Percent of screen fails	The number and percent of screen failures with the reason for screen failures (flap not viable etc.) will be tabulated and summarized.	Study Day 1 - 24 months