Phase 2 N=68 Diagnostic

New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome

Cushing Syndrome · Endocrine Disease

Bottom Line

View on ClinicalTrials.gov: NCT00001849 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jan 2021

Primary outcome: Primary: Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients — 96.3; 77.1; 66.7; 100 percentage of patients

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Pentetreotide (Drug); 18F-DOPA (Drug); CT scan (Device); MRI (Device); 18-FDG (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Primary completion: Apr 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients	96.3; 77.1; 66.7; 100; 45.1; 42.9	—
PRIMARY Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Specific Lesions	75.4; 67.3; 46.2; 95.8; 40.4; 40.9	—

Summary

Cushing Syndrome is an endocrine disorder causing an over production of the hormone cortisol. Cortisol is produced in the adrenal gland as a response to the production of corticotropin (ACTH) in the pituitary gland. Between 10% and 20% of patients with hypercortisolism (Cushing Syndrome) have ectopic production of the hormone ACTH. Meaning, the hormone is not being released from the normal site, the pituitary gland. In many cases the ectopic ACTH is being produced by a tumor of the lung, thymus, or pancreas. However, in approximately 50% of these patients the source of the ACTH cannot be found even with the use of extensive imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), and nuclear scans (111-indium pentetreotide). The ability of these tests to locate the source of the hormone production is dependent on the changes of anatomy and / or the dose and adequate uptake of the radioactive agent. The inability to detect the source of ectopic ACTH production often results in unnecessary pituitary surgery or irradiation. Unlike the previously described tests, positron emission tomography (PET scan) has the ability to detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This study will test whether fluorine-18-fluorodeoxyglucose (FDG), fluorine-18-dihydroxyphenylalanine (F-DOPA) or use of a higher dose of 111-indium pentetreotide can be used to successfully localize the source of ectopic ACTH production.

Eligibility Criteria

INCLUSION CRITERIA:

All eligible patients are invited to participate in this protocol. Patients are adults with possible ectopic Cushing syndrome. Since both men and women are affected with ectopic Cushing syndrome, both sexes are studied. All ethnic and racial groups are at risk and will be included. Patients must be willing to return to the National Institutes of Health (NIH) Clinical Center for follow-up studies.

EXCLUSION CRITERIA

Pregnant or lactating women. A pregnancy test is performed in women of childbearing potential (up to age 55) unless they have a history of hysterectomy.

Children (age less than18) 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.

Patients taking medications that alter CYP3A4 activity will not be eligible for the mifepristone study, since this P450 system metabolizes mifepristone. Such participants would receive a clinical high dose (18 mCi) octreoscan (H-OCT) instead, if the standard 6 mCi octreoscan (L-OCT) was negative. Patients with hypokalemia (K < 3.5 milliequivalent (mEq)/L) despite medical therapy with replacement or mineralocorticoid antagonists will also be excluded from the mifepristone studies.

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 or leg edema, and blood pressure over 190/100), abnormal coagulation (partial thromboplastin time or prothrombin time elevated by 30 percent above the normal values), hematopoietic (hematocrit less than 30 percent, hemoglobin below 10 g/dl, white count below 3000 K/microliter (UL), and platelets below 100,000 K/mm(3)), hepatic (liver enzymes elevated by 3-fold above normal values) or renal function (plasma creatinine level over 2.0).
impaired mental capacity or markedly abnormal psychiatric evaluation 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, of greater than 450 ml.
known allergy to 111-indium pentetreotide or other somatostatin analogues.
strong evidence for Cushing disease. This includes those with positive inferior petrosal sinus sampling or a lesion on pituitary MRI.

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Data sourced from ClinicalTrials.gov (NCT00001849). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.