Natural History of Familial Carcinoid Tumor

This study will evaluate members in families with a history of small bowel carcinoid cancer to study the natural history of those family members that have the disease, determine ways to improve early detection by performing surveillance on those at risk but without disease and to identify the gene(s) that may cause the tumors. Familial carcinoid tumors usually originate in hormone-producing cells that line the small intestine or other cells of the digestive tract. The tumors are slow-growing and usually take many years before they cause symptoms. It is known that these tumors occur more often in some families and are then passed from one generation to the next by inherited genes.

Members of families, including all siblings and offspring in which two or more immediate blood relatives have had small bowel carcinoid tumors are eligible for this study. In some cases unaffected spouses of family members diagnosed with carcinoid cancer are also requested to participate by donating a sample of blood only.

Participants undergo a medical evaluation every 3 years during a 3- to 5-day hospital stay at the NIH Clinical Center. All participants have a personal and family medical history obtained and undergo a physical examination, blood and urine tests.

People who already have a small bowel carcinoid tumor or are at risk of developing a carcinoid tumor have some or all of the following procedures to determine the presence of carcinoid tumor and its (omit next two words- location or) spread to other areas of the body:

• Video Capsule Endoscopy: Visualization of the gastrointestinal tract by ingesting a disposable, "vitamin-pill sized" video capsule that has its own camera and light source.
• CT of the chest abdomen and pelvis with oral and IV contrast : X-ray examination of the chest, abdominal and pelvis organs.
• 18 FDOPA Positron emission tomography (PET) with CT for localization: Nuclear imaging scan to look at tumor activity.
• MRI Liver with contrast - to determine if disease has spread to liver
• Gallium 68 PET/CT-limited to individuals that have residual tumor.
• Clinical and research blood work

Should mid gut carcinoid tumors be found every participant will be assisted in determine what the best course of treatment will be for them.

Study Overview

• Status: Recruiting
• Conditions: Carcinoid
• Intervention / Treatment: Drug: [18F]-DOPA

Detailed Description

Study Description:

This study is designed as a prospective evaluation for diagnostic screening, genotyping and natural history of participants belonging to kindreds with familial carcinoid tumor.

Objectives: Primary Objective:

Study the natural history of familial carcinoid tumors: incidence, age of onset, symptoms, the appropriate diagnostic (biochemical and imaging) modalities, location, histology and metastatic potential of the tumors, metabolic sequelae of the tumor, and clinical and biochemical prognostic factors.

Secondary Objectives:

• Screen for occult disease and determine whether early detection affects the natural history of the disease.
• Compare the sensitivity and specificity of various imaging tomography (CT) with IV contrast and oral Volumen, 18FDOPA PET/CT scan, [68Ga] DOTATATE PET/CT scan and endoscopic modalities for diagnosing and following carcinoid tumors.
• Collect tumor specimens for histologic evaluation, culturing of intestinal organoids, and genotyping (including DNA and RNA sequencing).
• Sequester DNA from peripheral blood for genotyping (including sequencing) with the intention of localizing a susceptibility gene/s responsible for the familial occurrence of the disease.

• Study Type: Observational
• Enrollment (Estimated): 1600

Contacts and Locations

• Study Contact: Name: Joanne Forbes, C.R.N.P.; Phone Number: (301) 443-9557; Email: forbesjo@mail.nih.gov
• Study Contact Backup: Name: Stephen A Wank, M.D.; Phone Number: (301) 496-4202; Email: stevew@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Community sample

Description

• INCLUSION CRITERIA:

There are four types of participants who will be included in this protocol as outlined below.

In order to be eligible to participate in this study, an individual must meet all of the following criteria for their group:

Group 1 (Arm 1 or Arm 2)

• Male and female subjects >= 18 years of age
• Have a diagnosis of small intestinal carcinoid tumor
• Have at least one blood relation with a diagnosis of either small intestinal, pulmonary, kidney or gastropancreatic neuroendocrine tumor or metastatic neuroendocrine tumor of unknown primary

Group 2 (Arm 1 or Arm 2)

• Male and female subjects >= 18 years of age
• Has multiple synchronous primary small intestinal tumors

Group 3 (Arm 1 or Arm 2)

• Male and female subjects >=18 years of age
• Does not have a diagnosis of carcinoid tumor

• Has one of the following:

  • at least two blood relatives with any combination of diagnoses of small intestinal carcinoid tumor, a pulmonary, kidney, gastropancreatic neuroendocrine tumor or metastatic neuroendocrine tumor of unknown primary OR
  • has at least one blood relative with multiple, synchronous primary small bowel tumors

Group 4 (Arm 2 only)

• Male and female subjects >= 18 years of age
• Not biologically related to the participating family but has offspring who is/are blood relative(s) of a participating subject.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this

study:

1. Members of families with multiple endocrine neoplasia (MEN) I, MEN II or other familial tumor syndromes such as Von Hippel Lindau Syndrome and Neurofibromatosis type I and type II for which there is a known genetic predisposition to non-carcinoid tumors as well as

   carcinoid tumors will be excluded from the study.

2. Any condition which, in the opinion of the investigator, would make it unsafe to participate or would prohibit completion of the protocol.
3. Inability to provide informed consent
4. Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm 1; Participants who undergo extended evaluation for disease at NIH	Drug: [18F]-DOPA
Arm 2; Participants who do not undergo extended screening or evaluation for disease at NIH	Drug: [18F]-DOPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study the natural history of familial carcinoid tumors	Incidence, age of onset, symptoms, the appropriate diagnostic (biochemical and imaging) modalities, location, histology and metastatic potential of the tumors, metabolic sequelae of the tumor, and clinical and biochemical prognostic factors	End of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the sensitivity and specificity of various imaging modalities: computed tomography (CT) with IV contrast and oral Volumen, 18F-DOPA PET/CT scan, [68Ga]DOTATATE PET/CT scan and endoscopic modalities for diagnosing and following carcinoid ...	Enrollment of a sufficient number of subjects to allow for the determination of sensitivity and specificity for each imaging and endoscopic modality to show statistically significant superiority for one modality relative to the others	End of study
Sequester DNA from peripheral blood for genotyping (including sequencing) with the intention of localizing a susceptibility gene/s responsible for the familial occurrence of the disease	Determination of the gene mutation responsible for the disease in each family	End of study
Collect tumor specimens for histologic evaluation, culturing of intestinal organoids, and genotyping (including DNA and RNA sequencing)	Sufficient number of tumors collected to correlate disease grade with natural history of disease and assess the variability in disease grade	End of study
Screen for occult disease and determine whether early detection affects the natural history of the disease	Change in survival	End of study

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Stephen A Wank, M.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Caplin ME, Buscombe JR, Hilson AJ, Jones AL, Watkinson AF, Burroughs AK. Carcinoid tumour. Lancet. 1998 Sep 5;352(9130):799-805. doi: 10.1016/S0140-6736(98)02286-7.
• Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003 Feb 15;97(4):934-59. doi: 10.1002/cncr.11105.
• Capella C, Heitz PU, Hofler H, Solcia E, Kloppel G. Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch. 1995;425(6):547-60. doi: 10.1007/BF00199342.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2008

Study Registration Dates

• First Submitted: March 26, 2008
• First Submitted That Met QC Criteria: March 26, 2008
• First Posted (Estimated): March 28, 2008

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: March 28, 2024

More Information

Terms related to this study

• Keywords: PET; Natural History; Serotonin; Gastrointestinal; Neuroendocrine; Carcinoid Tumor; Gastrointestinal Carcinoid Tumor; Familial Cancer Tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Carcinoid Tumor
• Other Study ID Numbers: 080098; 08-DK-0098

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No