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

  • STATUS
    Recruiting
  • End date
    Dec 31, 2030
  • participants needed
    80
  • sponsor
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Updated on 15 June 2022
ct scan
pituitary
positron emission tomography
mifepristone
dotatate
corticotropin
hypercortisolism
ectopic acth
scan mri

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.

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.

Details
Condition ACTH, Cushing's Syndrome
Treatment MRI, mifepristone, CT Scan, 18F-DOPA, F-DOPA PET Scan, Ga-DOTATATE, Octreoscan, CT, MRI, 68Ga-DOTATATE, DOTATATE PET-CT, F-DOPA PET CT, Routine MRI scan, Gated MRI scan
Clinical Study IdentifierNCT02019706
SponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Last Modified on15 June 2022

Eligibility

Yes No Not Sure

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
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