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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 : October 15, 2019
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
ACTH Cushing's Syndrome Drug: DOTATATE PET-CT Drug: F-DOPA PET CT Drug: OCTREOTIDE Radiation: CT Scan Device: MRI Phase 1 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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 : November 26, 2013
Estimated Primary Completion Date : December 31, 2030
Estimated Study Completion Date : December 31, 2030


Arm Intervention/treatment
Experimental: Imaging
All subjects will be imaged
Drug: DOTATATE PET-CT
68Ga-DOTATATE

Drug: F-DOPA PET CT
F-DOPA PET CT

Drug: OCTREOTIDE
OCTREOTIDE SCAN

Radiation: CT Scan
Routine CT scan

Device: MRI
Routine MRI and gated MRI




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


Secondary Outcome Measures :
  1. Conversion of a negative DOTATATE test to positive one after mifepristone [ Time Frame: Ongoing ]
  2. Is there a correlation between F-DOPA or DOTATATE uptake and type of tumor, size and proliferative activity [ Time Frame: Ongoing ]
  3. Is there a combination of tests with optimal diagnostic accuracy? [ Time Frame: Ongoing ]
  4. # lesions detected by gated chest MRI vs. routine MRI [ Time Frame: Ongoing ]


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
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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
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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
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Principal Investigator: Lynnette K Nieman, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional Information:
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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: October 15, 2019
Last Verified: October 9, 2019

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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:
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Cushing Syndrome
Syndrome
Disease
Pathologic Processes
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Octreotide
Gastrointestinal Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents