Prospective Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Ectopic Cushing Syndrome

NCT ID: NCT02019706

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-12
• Study Completion Date: 2030-12-31

Brief Summary

Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50% of these patients, the tumoral source of ACTH cannot be found initially despite very detailed and extensive imaging, including studies such as computed tomography, magnetic resonance imaging, and octreotide scan (Octreoscan) using the standard dose of indium- 111 pentetreotide ([111In-DTPA-D-Phe]-pentetreotide). The sensitivity and specificity of structurally based imaging studies depends on anatomic alterations and the size of the tumor. In contrast, positron emission tomography (PET) and somatostatin ligand imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This protocol tests the ability of [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, and the somatostatin imaging analogue, 68Ga-DOTATATE-PET, to localize the source of ectopic ACTH production.

Detailed Description

Study Description:

Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50% of these patients, the tumoral source of ACTH cannot be found initially despite very detailed and extensive imaging, including studies such as computed tomography, magnetic resonance imaging, and octreotide scan (Octreoscan) using the standard dose of indium- 111 pentetreotide ([111In-DTPA-D-Phe]-pentetreotide). The sensitivity and specificity of structurally based imaging studies depends on anatomic alterations and the size of the tumor. In contrast, positron emission tomography (PET) and somatostatin ligand imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue.

This protocol tests the ability of [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, and the somatostatin imaging analogue, 68Ga-DOTATATE-PET, to localize the source of ectopic ACTH production.

Objectives:

Primary Objectives:

• To determine which imaging technique (F-DOPA PET/CT, 68Ga-DOTATATE PET/CT, standard CT, and/or standard MRI) has the best sensitivity.
• To determine if there is a combination of imaging tests with optimal diagnostic accuracy.

Secondary Objective:

-To evaluate a potential correlation between 18F-DOPA or 68Ga-DOTATATE uptake and the type of tumor, its size, SSTR expression or proliferative activity.

Exploratory Objectives:

• To evaluate the ability of gated cardiac imaging with CT and MRI to improve the detection of retrocardiac lung lesions.
• To determine whether PET scans at an interval of less than one year localize tumors.

Endpoints:

Primary Endpoint:

-Imaging results and pathology of resected tumors

Secondary Endpoints:

-18F-DOPA or 68Ga-DOTATATE imaging results, tumor pathology, tumor size, proliferative index and SSTR expression.

Exploratory Endpoints:

• Gated cardiac imaging CT and/or MRI; all other imaging results, tumor pathology.
• Imaging results and pathology of resected tumors.

Conditions

ACTH; Cushing's Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Imaging

All subjects will be imaged

Group Type: EXPERIMENTAL

DOTATATE PET-CT

Intervention Type: RADIATION

68Ga-DOTATATE PET/CT

F-DOPA PET CT

Intervention Type: RADIATION

68Ga-DOTATATE PET/CT

CT scan

Intervention Type: RADIATION

routine CT scan

Routine MRI scan

Intervention Type: DIAGNOSTIC_TEST

routine 1.5 or 3T MRI scan

Gated MRI scan

Intervention Type: DIAGNOSTIC_TEST

Cardiac gated MRI scan

68Ga-DOTATATE

Intervention Type: DRUG

68Ga-DOTATATE radioligand

18F-DOPA

Intervention Type: DRUG

18F-DOPA radioligand

Interventions

DOTATATE PET-CT

68Ga-DOTATATE PET/CT

Intervention Type: RADIATION

F-DOPA PET CT

68Ga-DOTATATE PET/CT

Intervention Type: RADIATION

CT scan

routine CT scan

Intervention Type: RADIATION

Routine MRI scan

routine 1.5 or 3T MRI scan

Intervention Type: DIAGNOSTIC_TEST

Gated MRI scan

Cardiac gated MRI scan

Intervention Type: DIAGNOSTIC_TEST

68Ga-DOTATATE

68Ga-DOTATATE radioligand

Intervention Type: DRUG

18F-DOPA

18F-DOPA radioligand

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

To be eligible to participate in this study, an individual must meet all of the following criteria:

• 18 - 90 years of age
• Medical history of ectopic Cushing syndrome or diagnosed with the possibility of ectopic Cushing syndrome
• For females of reproductive potential: agreement to use highly effective contraception for at least 2 weeks before any PET scan
• Ability of subject to understand and the willingness to sign a written informed consent document
• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnancy or lactation; the radiation associated with PET and CT scans may be harmful to a developing fetus. Likewise the ingestion of radionuclides in breast milk has an unknown risk to an infant.
• Evidence of severe active infection
• Clinically significantly impaired cardiovascular function, abnormal coagulation in the absence of medically-indicated treatment (PT and PTT elevated by 30% above the normal values), hematopoietic (hematocrit less than 30%, hemoglobin below 10 g/dl, white count below 3000 K/UL, and platelets below 100,000 K/mm^3), hepatic (liver enzymes elevated by 4-fold above normal values), or renal function (plasma creatinine level over 2.1).
• Based on the clinical judgment of the attending physician, other medical problems may prompt exclusion.
• Body weight over 136 kg, which is the limit for the tables used in the scanning areas.
• Combined blood withdrawal during the six weeks preceding the study greater than 450 ml.
• Subjects who previously underwent ten or more F-DOPA PET/CT scans and ten or more DOTATATE scans.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lynnette K Nieman, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Raven N McGlotten, R.N.

Role: CONTACT

mcglottenr@mail.nih.gov

(301) 827-0190

Lynnette K Nieman, M.D.

Role: CONTACT

niemanl@mail.nih.gov

(301) 496-8935

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2014-CH-0028.html

NIH Clinical Center Detailed Web Page

Other Identifiers

14-CH-0028

Identifier Type: -

Identifier Source: secondary_id

140028

Identifier Type: -

Identifier Source: org_study_id