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

NCT00001849 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 99005599-CH-0055
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cushing Syndrome; Endocrine Disease

Keywords

PET; fluorine -18(18F)-DOPA; Pentetreotide; ACTH; Octreotide; Cushing's Syndrome; Ectopic Cushing Syndrome

Outcome Measures

Primary Outcomes (2)

• Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Patients

  The percentage of patients in whom imaging correctly identified an ACTH-secreting non-pituitary tumor within six months of resection or in which imaging identified a recurrence at a site of previous resection.

  six months or less

• Sensitivity of Imaging Modalities for the Detection of ACTH-secreting Non-pituitary Tumor in Specific Lesions

  The percentage of lesions for which imaging correctly identified an ACTH-secreting non-pituitary tumor within six months of resection or for which imaging identified a recurrence at a site of previous resection.

  six months or less

Study Arms (1)

Patients with Cushing Syndrome

EXPERIMENTAL

Patients receive various types of radiologic or nuclear medicine scans to identify tumor

Drug: Pentetreotide; Drug: 18F-DOPA; Device: CT scan; Device: MRI; Drug: 18-FDG

Interventions

Pentetreotide DRUG

Binds primarily to the somatostatin receptors subtypes (sst) 2 and 5. A high dose (18mCi) was used if the conventional dose (6mCi) was negative and scheduling was available. High doses limited to 3 over the course of the study.

Also known as: [111In-diethylenetriaminepentaacetic acid-D-Phe]-pentetreotide

Patients with Cushing Syndrome

18F-DOPA DRUG

18F-DOPA is a radiolabeled amino acid used as a radiotracer in positron emission tomography (PET). Limited to 3 doses over the course of the study.

Also known as: 6-fluoro-L-DOPA, 56494

Patients with Cushing Syndrome

CT scan DEVICE

CT scan of chest, abdomen, neck and /or pelvis

Also known as: computed tomography scan

Patients with Cushing Syndrome

MRI DEVICE

MRI scan of head/pituitary, chest, abdomen, neck and /or pelvis

Also known as: magnetic resonance imaging scan

Patients with Cushing Syndrome

18-FDG DRUG

FDG PET scan of body

Also known as: 18-fluorine fluorodeoxyglucose PET scan

Patients with Cushing Syndrome

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Findling JW, Tyrrell JB. Occult ectopic secretion of corticotropin. Arch Intern Med. 1986 May;146(5):929-33.

  PMID: 3963984 BACKGROUND

• Jex RK, van Heerden JA, Carpenter PC, Grant CS. Ectopic ACTH syndrome. Diagnostic and therapeutic aspects. Am J Surg. 1985 Feb;149(2):276-82. doi: 10.1016/s0002-9610(85)80085-4.

  PMID: 2982290 BACKGROUND

• Trainer PJ, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf). 1991 Apr;34(4):317-30. doi: 10.1111/j.1365-2265.1991.tb03773.x. No abstract available.

  PMID: 1879062 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cushing Syndrome; Endocrine System Diseases

Interventions

pentetreotide; fluorodopa F 18; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Fluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases

Intervention Hierarchy (Ancestors)

Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography; Deoxyglucose; Deoxy Sugars; Carbohydrates

Limitations and Caveats

Small number of subjects with this rare disorder; radiation safety risk limited number of some scans; difficulty in scheduling all scans due to lack of availability of slots or radionuclide.

Results Point of Contact

• Title: Lynnette Nieman MD
• Organization: NIDDK, NIH

NiemanL@nih.gov

301-496-8935

Study Officials

• Lynnette K Nieman, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Comparison of results in patients receiving similar imaging scans

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: May 20, 1999
• Primary Completion: April 26, 2019
• Study Completion: April 26, 2019
• Last Updated: April 14, 2021
• Results First Posted: January 25, 2021

Record last verified: 2020-01

Locations

US (1)