Feasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE

Meningioma Clinical Trial

Official title:

A Pilot Study to Evaluate Feasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06377371
• Other study ID #: 23-03025815
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2024
• Est. completion date: January 2025

Study information

• Verified date: May 2024
• Source: Weill Medical College of Cornell University
• Contact: Jana Ivanidze, MD/PhD
• Phone: 212-746-4587
• Email: jai9018[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study team hypothesizes that it is feasible to intraoperatively detect tumor following [CU64]DOTATATE injection using the gamma probe device.

Description:

Objectives:

Primary objectives: The primary objective of this pilot study is to evaluate the feasibility of intraoperative tumor detection using [Cu64]DOTATATE. The study team further wants to validate the gamma count measurements using pre- and post-operative Positron Emission Tomography (PET) standardized uptake value (SUV) .

Secondary Objectives: To correlate intraoperative tracing findings with from pathology markers ( World Health Organization grade (WHO grade), Ki-67, Somatostatin Receptor 2 expression (SSTR2A expression), Estrogen receptor expression (ER expression), Progesterone receptor expression (PR expression)) using samples obtained as part of routine surgical care. To evaluate the correlation of post resection gamma count with longitudinal PET follow up.

Exploratory objectives: To establish best practices for integration of intraoperative tumor tracing using the neoprobe into the surgical workflow. To determine surgical candidates who will benefit most from intraoperative tracing based on tumor location, MRI features, etc.

Overall Design:

This is a single-center prospective observational pilot study to determine the feasibility of using [Cu64]DOTATATE for intraoperative tumor detection. 20 patients diagnosed with meningioma by conventional magnetic resonance imaging (MRI) who are candidates for surgical resection will be enrolled. Enrollment will be facilitated by colleagues in the neurosurgery department (also co- investigators on this study) with whom the PI has had several years of collaboration and an ongoing referral stream (6pprox.. 5 patients per week).

Patients will subsequently undergo pre-operative [Cu64]DOTATATE PET/MRI 12-24 hours prior to surgery. Given that [Cu64]DOTATATE has a much longer half-life compared to [Ga68]DOTATATE, it is uniquely suited for this application, allowing the patient to be injected once with the clinically approved dose, undergo immediate Positron Emission tomography scan and magnetic resonance imaging scan (PET/MRI) or Positron Emission tomography scan and computed tomography scan (PET/CT), and undergo resection the following day with sufficient radiotracer in situ for radio-guided surgery (RGS).

During the operation, the neurosurgeon will make a number of measurements using the neoprobe (available at our institution and currently in frequent routine clinical use for intraoperative sentinel node detection; commonly used for breast cancer, melanoma, oral cancer):

1. After exposing the tumor, and immediately before removal, tumor counts will be documented with the neoprobe. This count will be correlated with preoperative [Cu64]DOTATATE SUV to evaluate the relationship between radiographic radiotracer uptake and intraoperative radioactivity of the tumor.

2. After removing all tumor that can be removed safely, the surgeon will grade whether they feel they obtained a gross total resection (GTR) or whether tumor was left behind (subtotal resection (STR), e.g. because the surgeon had to leave behind tumor attached to critical structure). In case of STR, the neoprobe will be used to measure counts in the remaining tumor. In case of presumed GTR, the neoprobe will be used to measure counts in the resection cavity. This second count will be correlated with post-operative [Cu64]DOTATATE SUV to evaluate the effectiveness of this method in evaluating residual tumor.

These steps will not alter the regular course of the surgery in any way. Patients will have two follow-up points after the surgery: 1) at 6 weeks to 3 months post-op and 2) at 6 months to 12 months post-op. Patients will be clinically examined and will undergo repeat [Cu64]DOTATATE PET/MRI or PET/CT during these follow up visits, as standard of care, with radiotracer dosage being funded by the study for the 1st follow up scan, and determined standard of care for the 2nd follow up scan.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• High suspicion of meningioma necessitating surgical resection based on conventional MRI criteria, or diagnosis of meningioma based on pathology reports from prior resection with radiographic findings of suspected recurrent or residual tumor necessitating repeat surgery.

Exclusion Criteria:

• Pregnant or breastfeeding

• Patients undergoing endoscopic endonasal resection, eyebrow incision surgery, or any surgical procedure in which the neoprobe cannot be employed

• Patients with hypersensitivity to somatostatin analogs

• Patients with contraindications to conventional MRI

• Patients with prior history of cranial radiation therapy

• Patients currently enrolled in other therapeutic clinical trials related to meningioma will be excluded

Related Conditions & MeSH terms

• Meningioma

Intervention

Diagnostic Test:
• Brain Imaging with [Cu64]DOTATATE
Patients will undergo a [Cu64]DOTATATE PET/MRI or PET/CT before undergoing radio- guided surgery. Patients will undergo another [Cu64]DOTATATE PET/MRI or PET/CT 6 weeks- 3 months after their surgery, and 6 months- 12 months after surgery.

Procedure:
• Radio-guided Surgery With Neoprobe Utilization
After the subjects undergo the preoperative [Cu64]DOTATATE PET/MRI, subjects will undergo radio-guided surgery in which the surgeon will utilize a standard intraoperative gamma probe (Neoprobe Gamma Detection System ®) to assess primary/residual tumor detection.

Locations

Country	Name	City	State
United States	New York-Presbyterian/Weill Cornell Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Curium US LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Preoperative [Cu64]DOTATATE PET SUV	preoperative lesion [Cu64]DOTATATE PET SUV	At time of enrollment
Primary	1st Post-operative [Cu64]DOTATATE PET SUV	6 weeks to 3 months follow up post operative [Cu64]DOTATATE PET SUV	3 months
Primary	2nd Post-operative [Cu64]DOTATATE PET SUV	6 months to 12 months follow up post operative [Cu64]DOTATATE PET SUV	1 year
Primary	MRI Size Measurements	preoperative size measurements based on Response Assessment in Neuro-Oncology (RANO) guidelines	At time of enrollment
Primary	GTR vs STR Assessment	postoperative MRI-based assessment of GTR versus STR by a neuroradiologist, as determined by the presence or absence of nodular dural-based enhancement on post contrast 3D T1-weighted MR imaging and direct comparison to preoperative MRI.	6 weeks- 3 months
Primary	MRI Progression Assessment	follow-up MRI assessment of progression based on RANO guidelines	6-12 months
Primary	Target Lesion Neoprobe Count	Neoprobe count of the target lesion prior to resection.	At time of enrollment
Primary	Subtotal Neoprobe Count	Neoprobe count of the subtotally resected tumor or the resection cavity in case of presumed GTR post resection.	At time of enrollment
Primary	Reference Background Neoprobe Count	Neoprobe count of the reference background measured at least 1 cm away from the tumor (measured in at least two locations depending on the operative field)	At time of enrollment
Secondary	SSTR2 expression	immunohistochemistry analysis of SSTR2 expression in the resected tumor	At time of clinical neuropathological evaluation of resected tumor tissue (Immediate postoperative setting).
Secondary	WHO grade	determined histomorphologically based on pathologist's assessment of resected tumor tissue.	At time of clinical neuropathological evaluation of resected tumor tissue (Immediate postoperative setting).
Secondary	Ki67 Proliferation Index	Ki67 Proliferation Index (percentage of positively stained tumor cells among the total number of malignant cells assessed).	At time of clinical neuropathological evaluation of resected tumor tissue (Immediate postoperative setting).
Secondary	ER/PR expression	determined based on pathologist's assessment of resected tumor tissue.	At time of clinical neuropathological evaluation of resected tumor tissue (Immediate postoperative setting).