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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
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) )
ClinicalTrials.gov Identifier:
NCT02019706
First received: December 21, 2013
Last updated: March 14, 2014
Last verified: November 2013
  Purpose

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 Intervention Phase
Cushing Syndrome
Drug: F-DOPA PET Scan
Drug: Mifepristone
Drug: Ga-DOTATATE
Drug: Octreoscan
Other: CT, MRI
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Which imaging technique (TATA PET/CT, Ga-DOTATATE PET/CT, OCT, CT and MRI) has the best sensitivity? [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: November 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: F-DOPA PET Scan
    N/A
    Drug: Mifepristone
    N/A
    Drug: Ga-DOTATATE
    N/A
    Drug: Octreoscan
    N/A
    Other: CT, MRI
    N/A
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 [(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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02019706

Contacts
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 Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Lynnette K Nieman, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( 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
Study First Received: December 21, 2013
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cushing Syndrome
Ectopic ACTH Secretion
Imaging

Additional relevant MeSH terms:
Cushing Syndrome
Cardiac Complexes, Premature
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Dihydroxyphenylalanine
Mifepristone
Octreotide
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
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

ClinicalTrials.gov processed this record on August 20, 2014