Improving diagnosis and treatment of pheochromocytoma

Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

This study is testing new ways to find and treat pheochromocytomas, which are tumors from the adrenal glands, to help improve care for people with this condition.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3000 (estimated)
• Ages: 3 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: radiation
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT00004847 on ClinicalTrials.gov

What this trial studies

This study aims to enhance the methods for diagnosing, localizing, and treating pheochromocytomas, which are tumors that typically arise from the adrenal glands and can cause severe health issues due to the release of catecholamines. Participants will undergo a series of tests, including blood, urine, and imaging studies, to detect the presence of these tumors. If a tumor is identified, surgical options will be considered, while patients with multiple tumors may receive alternative evaluations. The study also investigates the genetic and molecular factors associated with these tumors to improve understanding and treatment strategies.

Who should consider this trial

Good fit: Ideal candidates include adults and children aged 3 years and older with known or suspected pheochromocytoma or paraganglioma, particularly those with elevated catecholamine levels or a family history of these tumors.

Not a fit: Patients with metastatic disease or those who do not have a confirmed diagnosis of pheochromocytoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more accurate diagnoses and better treatment options for patients with pheochromocytoma, potentially reducing the risk of severe complications.

How similar studies have performed: Other studies have shown promise in improving diagnostic methods for pheochromocytoma, but this approach may include novel genetic and molecular investigations.

Eligibility criteria

* INCLUSION CRITERIA:

Patients are eligible for inclusion in this study if they are adults or children of age 3 years old and up with known, sporadic or familial PHEO/PGL, on the basis of one or more of the following:

1. High levels of blood or urinary catecholamines, metanephrines, methoxytyramine or chromogranin A.
2. Highly suspected presence of PHEO/PGL based on imaging studies, even with normal biochemistry.
3. Personal or family history of PHEO/PGL or genetic pathogenic variants known to predispose individuals to develop PHEO/PGL.

Signed informed consent is required. The informed consent may be signed by the patient, parent/guardian in pediatric patients or legally authorized representative (LAR) in adults who lack-decision making capacity to consent to research participation.

Patients must have an outside general practitioner or endocrinologist. Patients with metastatic disease must also have an outside oncologist.

Family Members of Patients Arm (Linkage Analysis)

Participants are eligible for inclusion in this study arm if they are:

* Adult family members of patients enrolled in this study;
* The index family member in this study has a suspected hereditary PHEO/PGL based on previous genetic testing and other suspicious hereditory patterns such as family history of multiple individuals with PHEO/PGL; early age of disease onset; multiplicity of primary tumors; recurrence, etc. and
* Signed informed consent form is required

EXCLUSION CRITERIA:

Potential patients will be excluded on the basis of one or more of the following:

1. Pregnant or breastfeeding women
2. Severe cardiac dysfunction
3. Currently on dialysis

A pregnancy test is performed in women of childbearing age (up to age 55) as a screening after consenting. If a patient is found to have a positive pregnancy test, her participation in this protocol will be terminated. The patient can enroll or re-enroll in the protocol when she is no longer pregnant or breastfeeding.

In-person participating patients who are not willing to return to the NIH (e.g., after surgery or an initial evaluation) for more than 2 years may be removed from the protocol.

SPECIFIC INCLUSION/EXCLUSION CRITERIA FOR IMAGING STUDIES WITHIN OUR PROTOCOL:

In adult patients (Excludes Linkage Analysis Arm)

Imaging studies are not done in patients that have the following exclusion criteria:

* Inability to lie still for the entire imaging time (e.g., cough, severe arthritis, etc.).
* Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (e.g., severe claustrophobia, radiation phobia, etc.)
* Any additional medical conditions, serious illness, or other extenuating circumstance that, in the opinion of the Principal Investigator, may significantly interfere with study compliance.

In pediatric patients:

Inclusion criteria for research PET imaging in children:

* Children over 10 years old with very high suspicion of sporadic or familial PHEO/PGL based on at least one of the following:

  * The presence of new onset of symptoms typical of PHEO/PGL such as hypertension or hypertensive episodes, sweating, headaches, pallor, palpitations, drug resistant hypertension, etc.
  * Family history of PHEO/PGL or genetic pathogenic variants known to predispose individuals to develop these tumors.
  * The presence of a tumor on conventional imaging including ultrasound, CT and/or MRI or \[123I\]-MIBG or PET imaging not limited to \[18F\]-FDG.
* Children must give informed assent and be willing to return to the NIH for follow-up.

Exclusion criteria for research PET imaging in children:

* Children of less than 10 years of age.
* Children with impaired mental capacity that precludes informed assent.
* Inability to lie still for the entire imaging time (e.g., cough, turbulent children, severe claustrophobia, etc.).

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Catherine M Gordon, M.D. — Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Study coordinator: Alberta Derkyi, C.R.N.P.

Conditions Pheochromocytoma; Endocrine Disease; Endocrine Diseases; Genetics; Metanephrines; PET; Catecholamines