68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors. (DOMINO-START)

68Ga(Gallium)-DOTATATE Positron Emission Tomography (PET)/MRI in the Diagnosis and Management of Somatostatin Receptor Positive Central Nervous System CNS Tumors.

The study population consists of patients who undergo resection for somatostatin receptor-positive (SSTR-positive) CNS tumors, focusing on meningioma, and including esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and SSTR-positive systemic cancers metastatic to the brain, such as small cell carcinoma of the lung. The study indication is to determine the diagnostic utility of 68Ga-DOTATATE PET/MRI in the diagnosis and management of patients with SSTR-positive CNS tumors, specifically whether 68Ga-DOTATATE PET/MRI demonstrates utility distinguishing between tumor recurrence and post-treatment change. To date, the utility of Ga-68-DOTATATE PET/MRI in meningioma has not been explored. Investigators have over the past 3 months been able to accrue the largest case series of presently 12 patients in whom Ga-68-DOTATATE PET/MRI demonstrated utility in the assessment of meningioma, including assessment for postsurgical/postradiation recurrence, detection of additional lesions not visualized on MRI alone, and evaluation of osseous invasion. Based on this initial experience, investigators intend to study the impact of Ga-68-DOTATATE PET/MRI in the assessment of the extent of residual tumor in patients status post meningioma resection, specifically in patients in whom tumor location limits resectability, patients with World Health Organization (WHO) grade II/III disease, and patients with history of stereotactic radiosurgery (SRS) who develop postradiation change.

Study Overview

• Status: Recruiting
• Conditions: Pituitary Adenoma; Medulloblastoma; Meningioma; Esthesioneuroblastoma; Paraganglioma; CNS Tumors; Hemangioblastoma
• Intervention / Treatment: Diagnostic test: Ga68-DOTATATE-PET/MRI

Detailed Description

Prior to the onset of this study, the utility of Ga-68-DOTATATE PET/MRI in meningioma had not been explored. The investigator's pilot study serving as the basis for the proposed protocol resulted in the - to the investigators' knowledge - largest case series of 21 patients in whom Ga-68 DOTATATE PET/MRI demonstrated utility in the assessment of meningioma, including assessment for postsurgical/postradiation recurrence, detection of additional lesions not visualized on MRI alone, and evaluation of osseous invasion. Based on this initial experience, investigators continued to study the impact of Ga-68-DOTATATE PET/MRI in the assessment of the extent of residual tumor in patients status post meningioma resection, specifically in patients in whom tumor location limits resectability, patients with WHO grade II/III disease, and patients with history of SRS who develop postradiation change.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jana Ivanidze, MD/Ph.D; Phone Number: 212-746-4587; Email: jai9018@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
      • Contact: Jana Ivanidze, MD/Ph.D; Phone Number: 212-746-4587; Email: jai9018@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

The patient cohort will consist of individuals who undergo resection for SSTR-positive CNS tumors, including meningioma, esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and SSTR-positive tumors metastatic to the brain, and in whom tumor recurrence versus post treatment change is questioned for reasons including, but not limited to, high WHO grade, suspected subtotal resection based on tumor location, or positive surgical margins. Subjects with diagnosis of meningioma specifically in patients in whom tumor location limits gross total resectability (for example in the skullbase, sphenoid wing, spheno-orbital location) and patients who have WHO grade II/ III disease.

Additionally, patients undergoing clinical Ga-68-DOTATATE or Cu-64-DOTATATE PET/MR or PET/CT will be followed via prospective chart review.

Description

Inclusion Criteria:

• ≥ 18 years of age
• Diagnosis of meningioma based on pathology reports and suspected recurrence or residual disease based on standard-of-care MRI
• Additionally, patients with other somatostatin receptor 2 positive brain tumors, including esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma, and SSTR-positive systemic cancers metastatic to the brain will be considered for the purposes of obtaining feasibility data
• As the investigator's institution, PET/MRI scanner utilizes a 3 Tesla (T) magnet, patients who may be ineligible to undergo 3T MRI but may undergo 1.5 Tesla (T) MRI, will undergo a 1.5T MRI as per clinical standard-of-care and a Ga68-DOTATATE PET/CT with the PET portion to be fused with the 1.5T MRI utilizing fusion software.

Exclusion Criteria:

• Contraindications to gadolinium-based contrast agent
• History of allergic reaction to Gallium-68-DOTATATE
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Meningioma; Cohort of 30 subjects with meningioma.	Diagnostic test: Ga68-DOTATATE-PET/MRI; In patients with meningioma who are undergoing surgical planning, subjects will undergo a PET scan at the time of their pretreatment or preoperative standard of care MRI exam, prior to surgery performed for research purposes. Instead of the standard of care MRI exam, subjects will undergo a dedicated hybrid Gallium-68-DOTATATE PET/MRI.There will be up to two follow-up with Ga68-DOTATATE PET/MRI scans performed as standard of care. In patients with SSTR-positive CNS tumors that are non-meningioma, MRI is often performed to assess extent of disease. Subjects may be asked to undergo a PET scan for research purposes at the time of their standard of care MRI. Instead of the standard of care MRI exam, they may be asked to undergo a dedicated hybrid Gallium-68-DOTATATE PET/MRI.
Other: Non-Meningioma; Cohort of 60 subjects with non-meningioma: (esthesioneuroblastoma, hemangioblastoma, medulloblastoma, paraganglioma, pituitary adenoma and SSTR-positive tumors metastatic to the brain)	Diagnostic test: Ga68-DOTATATE-PET/MRI; In patients with meningioma who are undergoing surgical planning, subjects will undergo a PET scan at the time of their pretreatment or preoperative standard of care MRI exam, prior to surgery performed for research purposes. Instead of the standard of care MRI exam, subjects will undergo a dedicated hybrid Gallium-68-DOTATATE PET/MRI.There will be up to two follow-up with Ga68-DOTATATE PET/MRI scans performed as standard of care. In patients with SSTR-positive CNS tumors that are non-meningioma, MRI is often performed to assess extent of disease. Subjects may be asked to undergo a PET scan for research purposes at the time of their standard of care MRI. Instead of the standard of care MRI exam, they may be asked to undergo a dedicated hybrid Gallium-68-DOTATATE PET/MRI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate whether Ga-68-DOTATATE PET/MRI provides additional clinical benefit	Diagnostic accuracy of Ga-68-DOTATATE PET/MRI will be compared to MRI alone. Correlative analyses will be performed including logistic regression/ Spearman correlation for continuous variables, and Mann-Whitney U tests for not normally distributed subgroups for variables allowing for dichotomization.	Longitudinal assessment up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlate Ga-68-DOTATATE PET/MR findings with histopathologic biomarker, SSTR2 expression	Histopathologic biomarkers, including SSTR2 expression will be assessed for patients with meningioma, who undergo resection. Correlative analyses will be performed including logistic regression/ Spearman correlation for continuous variables, and Mann-Whitney U tests for not normally distributed subgroups for variables allowing for dichotomization.	Longitudinal assessment up to 10 years
Correlate Ga-68-DOTATATE PET/Magnetic Resonance(MR) findings with histopathologic biomarker, Ki67	Histopathologic biomarkers, including Ki67 will be assessed for patients with meningioma, who undergo resection. Correlative analyses will be performed including logistic regression/ Spearman correlation for continuous variables, and Mann-Whitney U tests for not normally distributed subgroups for variables allowing for dichotomization.	Longitudinal assessment up to 10 years
Correlate Ga-68-DOTATATE PET/MR findings with histopathologic biomarker, progesterone receptor	Histopathologic biomarkers, including progesterone receptor will be assessed for patients with meningioma, who undergo resection. Correlative analyses will be performed including logistic regression/ Spearman correlation for continuous variables, and Mann-Whitney U tests for not normally distributed subgroups for variables allowing for dichotomization.	Longitudinal assessment up to 10 years
Correlate Ga-68-DOTATATE PET/MR findings with histopathologic biomarker, epidermal growth factor receptor (EGFR)	Histopathologic biomarkers, including EGFR will be assessed for patients with meningioma, who undergo resection. Correlative analyses will be performed including logistic regression/ Spearman correlation for continuous variables, and Mann-Whitney U tests for not normally distributed subgroups for variables allowing for dichotomization.	Longitudinal assessment up to 10 years

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Jana Ivanidze, MD/Ph.D, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Kim SH, Roytman M, Madera G, Magge RS, Liechty B, Ramakrishna R, Pannullo SC, Schwartz TH, Karakatsanis NA, Osborne JR, Lin E, Knisely JPS, Ivanidze J. Evaluating diagnostic accuracy and determining optimal diagnostic thresholds of different approaches to [68Ga]-DOTATATE PET/MRI analysis in patients with meningioma. Sci Rep. 2022 Jun 3;12(1):9256. doi: 10.1038/s41598-022-13467-9.
• Ivanidze J, Roytman M, Skafida M, Kim S, Glynn S, Osborne JR, Pannullo SC, Nehmeh S, Ramakrishna R, Schwartz TH, Knisely JPS, Lin E, Karakatsanis NA. Dynamic 68Ga-DOTATATE PET/MRI in the Diagnosis and Management of Intracranial Meningiomas. Radiol Imaging Cancer. 2022 Mar;4(2):e210067. doi: 10.1148/rycan.210067.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2019
• Primary Completion (Estimated): December 31, 2038
• Study Completion (Estimated): December 31, 2038

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• 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; Endocrine System Diseases; Endocrine Gland Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Nervous System Neoplasms; Cranial Nerve Diseases; Neuroendocrine Tumors; Hemangioma; Neoplasms, Vascular Tissue; Neuroectodermal Tumors, Primitive; Pituitary Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Meningeal Neoplasms; Olfactory Nerve Diseases; Hemangioma, Capillary; Neuroblastoma; Adenoma; Pituitary Neoplasms; Central Nervous System Neoplasms; Medulloblastoma; Meningioma; Esthesioneuroblastoma, Olfactory; Paraganglioma; Hemangioblastoma
• Other Study ID Numbers: 1807019445

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No