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

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ClinicalTrials.gov Identifier: NCT02019706
Recruitment Status : Recruiting
First Posted : December 24, 2013
Last Update Posted : July 23, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

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
Cushing Syndrome Drug: F-DOPA PET Scan Drug: Mifepristone Drug: Ga-DOTATATE Drug: Octreoscan Other: CT, MRI 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 ([(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 [18F]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, Octreoscan and another somatostatin imaging analogue, 68Ga-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 68Ga-DOTATATE PET/CT.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
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
Study Start Date : November 26, 2013
Estimated Primary Completion Date : August 15, 2018
Estimated Study Completion Date : August 15, 2018





Primary Outcome Measures :
  1. Which imaging technique (TATA PET/CT, Ga-DOTATATE PET/CT, OCT, CT and MRI) has the best sensitivity? [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Adults with possible ectopic Cushing syndrome
  • Age 18-90
  • 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) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02019706


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, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Lynnette K Nieman, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional Information:
Publications:
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT02019706     History of Changes
Other Study ID Numbers: 140028
14-CH-0028
First Posted: December 24, 2013    Key Record Dates
Last Update Posted: July 23, 2018
Last Verified: July 16, 2018

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
Cushing Syndrome
Ectopic ACTH Secretion
Imaging

Additional relevant MeSH terms:
Cardiac Complexes, Premature
Disease
Adrenal Gland Diseases
Endocrine System Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Syndrome
Cushing Syndrome
Pathologic Processes
Adrenocortical Hyperfunction
Octreotide
Mifepristone
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents