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

• ClinicalTrials.gov Identifier: NCT02019706
• Recruitment Status: Recruiting
• First Posted: December 24, 2013
• Last Update Posted: March 13, 2023
• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Study Description

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 ([(111)In-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 (like octreotide) imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This protocol tests the ability of [(18)F]-L-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET, Octreoscan and another somatostatin imaging analogue, (68)Ga-DOTATATE-PET, to localize the source of ectopic ACTH production. The study also examines whether administration of the glucocorticoid antagonist mifepristone can improve the sensitivity of the (68)Ga-DOTATATE PET/CT.

Condition or disease	Intervention/treatment	Phase
ACTH; Cushing's Syndrome	Radiation: DOTATATE PET-CT; Radiation: F-DOPA PET CT; Radiation: CT scan; Diagnostic Test: Routine MRI scan; Diagnostic Test: Gated MRI scan; Drug: 68Ga-DOTATATE; Drug: 18F-DOPA	Phase 2

Detailed 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 (like octreotide) 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Patients With Ectopic Cushing Syndrome
• Actual Study Start Date: February 12, 2014
• Estimated Primary Completion Date: December 31, 2030
• Estimated Study Completion Date: December 31, 2030

Arms and Interventions

Arm	Intervention/treatment
Experimental: Imaging; All subjects will be imaged	Radiation: DOTATATE PET-CT; 68Ga-DOTATATE PET/CT; Radiation: F-DOPA PET CT; 68Ga-DOTATATE PET/CT; Radiation: CT scan; routine CT scan; Diagnostic Test: Routine MRI scan; routine 1.5 or 3T MRI scan; Diagnostic Test: Gated MRI scan; Cardiac gated MRI scan; Drug: 68Ga-DOTATATE; 68Ga-DOTATATE radioligand; Drug: 18F-DOPA; 18F-DOPA radioligand

Outcome Measures

Primary Outcome Measures :

1. Which imaging technique best detects ectopic ACTH-producing tumors [ Time Frame: 6-12 months ]
   Subjects will be imaged every 6-12 months until tumor is found
2. Is there a combination of tests with optimal diagnostic accuracy? [ Time Frame: 6-12 months ]
   subjects will be imaged every 6-12 months until tumor is found

Secondary Outcome Measures :

1. Is there a correlation between F-DOPA or DOTATATE uptake and type of tumor, size and proliferative activity [ Time Frame: Ongoing ]
2. Number lesions detected by gated chest MRI vs. routine MRI [ Time Frame: Ongoing ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:
• Adults with possible ectopic Cushing syndrome
• Age 18-80
• Patients must be willing to return to NIH for follow-up studies.

EXCLUSION CRITERIA:

• Pregnant or lactating women. A pregnancy test is performed in women of childbearing potential (up to age 55) prior to each MRI or study involving radiation, unless they have a history of hysterectomy and/or bilateral oophorectomy.
• Children (age less than 18) are excluded. Because ectopic ACTH secretion is rare in this age group, the likelihood of benefit is less and does not balance the risk of radiation.
• Very elderly patients (> 90 years)
• For the mifepristone studies only: Patients taking medications that alter CYP3A4 activity will not be eligible for the mifepristone study, since this P450 system metabolizes mifepristone. Patients with hypokalemia (K < 3.5 mEq/L), despite medical therapy with replacement or mineralocorticoid antagonists will also be excluded from the mifepristone studies. Such patients may participate in other components of the protocol. Medications affecting CYP3A4 may be adjusted to allow participation in the mifepristone component, with a one week washout period.
• The presence of severe active infection.
• clinically significantly impaired cardiovascular (e.g. history of abnormally low ejection fraction, the presence of moderate pulmonary fluid overload, and/or blood pressure over 190/100), 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.
• impaired mental capacity or markedly abnormal psychiatric condition that precludes informed consent.
• 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 450 ml.
• known allergy to [(111)In-DTPA-D-Phe]-pentetreotide or other somatostatin analogues.
• strong evidence for Cushing s disease. This includes those with a central to peripheral ACTH gradient during IPSS or a lesion on pituitary MRI. We anticipate that these exclusion criteria will increase the ratio of patients with ectopic ACTH syndrome to those with Cushing s disease from the usual 1: 8 to 1: 2, thus we would accrue 3 patients to identify one with ectopic ACTH secretion.

Contacts and Locations

Contacts

Contact: Raven N McGlotten, R.N.; (301) 827-0190; mcglottenr@mail.nih.gov

Contact: Lynnette K Nieman, M.D.; (301) 496-8935; niemanl@mail.nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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

Investigators

• Principal Investigator: Lynnette K Nieman, M.D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• ClinicalTrials.gov Identifier: NCT02019706
• Other Study ID Numbers: 140028; 14-CH-0028
• First Posted: December 24, 2013
• Last Update Posted: March 13, 2023
• Last Verified: March 9, 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: .On request, IPD related to a publication will be made available.
• Supporting Materials: Clinical Study Report (CSR); Analytic Code
• Time Frame: Start at the time of publication, for five years unless the study investigators leave NIH
• Access Criteria: The PI will review requests and will provide data to investigators who wish to perform meta-analysis with other manuscript results. Data will be provided as an anonymized excel spread sheet.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):

DOTATATE; Cushing's Syndrome; Hypercortisolism

Additional relevant MeSH terms:

Cushing Syndrome; Syndrome; Disease; Pathologic Processes; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Dihydroxyphenylalanine; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs