Neoplasms

Symptoms and General Pathology

All Conditions

Rare Diseases

Neoplasm Metastasis

Pheochromocytoma

Paraganglioma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Paragangliomas 1

Neuroendocrine Tumor

Neuroepithelioma

Anti-Dyskinesia Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Dermatologic Agents

Amino Acids

Carbidopa

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Tretinoin

3-Iodobenzylguanidine

alpha-Methyltyrosine

Enzyme Inhibitors

Radiopharmaceuticals

Tyrosine

[131]I-MIBG

6-[18F]Fluorodopamine

[123]I-MIBG

This study will evaluate the effectiveness of 131MIBG in treating malignant pheochromocytoma and whether sensitization medications improve the response to treatment. Pheochromocytoma is a rare type of tumor that usually occurs in the adrenal glands. The tumor cells release chemicals like adrenaline that can cause large increases in blood pressure and pulse rate, with serious health consequences. Tumor in the adrenal glands usually can be removed surgically, but if the pheochromocytoma is malignant-i.e., has spread to many sites in the body-or is located in places where surgery is difficult or impossible, no satisfactory treatment is available. 131MIBG is a combination of an adrenaline-like chemical and a radioactive form of iodine. The 131MIBG attaches to the tumor cells and the high concentration of radioactive iodine kills them. Previous studies using 131MIBG to treat pheochromocytoma had a 36% response rate in terms of complete or partial improvement. This study will examine whether adding other sensitization medications to the 131MIBG treatment regimen will enhance its effectiveness in reducing the size and number of tumors.

Patients 18 years of age and older with malignant or inoperable pheochromocytoma may be eligible for this 18-month study. Candidates will be screened with various tests and procedures, which may include a medical history, physical examination, blood and urine tests, lung function studies, electrocardiogram, echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and bone scans and other scans using radioactive MIBG and octreotide.

Participants will be randomly assigned to one of two treatment groups: 1) 131MIBG plus sensitization medications, or 2) 131MIBG alone. All patients will be hospitalized 3 to 5 days for each 131MIBG treatment. The drug will be infused through a vein (intravenously, or I.V.) over 10 to 30 minutes. Patients will receive up to 3 treatments, separated by at least 3 months. All patients will also take potassium to protect the thyroid gland from radioactive iodine generated by the 131MIBG. The potassium is taken twice a day for 30 days, beginning the day before the 131MIBG treatment. Patients in the sensitization group will receive the following additional drugs for sensitization: methylprednisolone, intravenously a few minutes before 131MIBG treatment; Roaccutan, by mouth (capsules) twice a day for 6 weeks before treatment; Demser, by mouth 3 times a week for 1 week before treatment, and Carbidopa, by mouth every 6 hours for 4 days before treatment.

After each treatment, patients will have a clinical evaluation and periodic blood tests to check for adverse side effects of radiotherapy. Follow-up visits at NIH will be scheduled at 12 and 18 months after the first 131MIBG treatment for clinical, laboratory and imaging tests. Patients who had tumors in the lungs before treatment will have lung function tests 1, 3, and 6 months after each treatment. CT, MRI 131MIBG, and PET scanning will be done 1 week before each treatment.

Patients who have tumors that have grown by more than 25% and none that have shrunk by more than 50% or who have developed one or more new tumors while on 131MIBG treatment will be taken off the study.

Pheochromocytomas are tumors of chromaffin cells that synthesize catecholamines. This project tests the efficacy of radiotoxic treatment of malignant pheochromocytoma using (131)I-metaiodobenzylguanidine \[(131)I-MIBG\], and in particular, tests whether pre-treatment with enhancer pharmaceuticals increases the efficacy of experimental (131)I-MIBG treatment in reducing the size and number of tumors and the tumor burden.

131MIBG to Treat Malignant Pheochromocytoma

(131)I-Metaiodobenzylguanidine Treatment of Malignant Pheochromocytoma

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

James C. Reynolds, M.D./National Institute of Child Health and Human Development

Heart and Blood Diseases

Nervous System Diseases

Hypertension

Autonomic Nervous System Diseases

Primary Dysautonomias

Vasoconstrictor Agents

Respiratory System Agents

Cardiotonic Agents

Epinephrine

Norepinephrine

Dopamine

Racepinephrine

Epinephryl borate

This study involves sampling blood from both normal volunteers and patients with diseases known or suspected to involve body chemicals called catecholamines. The blood will be used to establish normal values for plasma levels of catecholamines and related neurochemicals; to test for abnormal neurochemical patterns in patients; and to establish a "bank" of DNA from normal volunteers and from patients to be used in future studies about possible alterations of catecholamine-related genes.

Study participants will report to NIH after fasting overnight except for water or noncaloric, noncaffeinated beverages. They must not have taken Tylenol for at least 5 days. Blood will then be drawn. DNA will be extracted and stored in the freezer for future studies.

This project is to allow blood sampling from normal volunteers and patients with dysautonomia, pheochromocytoma, hypertension, or neurogenetic diseases involving catecholaminergic systems. The blood is used to establish normal values for plasma levels of catechols and related neurochemicals; test for abnormal neurochemical patterns in patients; and establish a "bank" of DNA samples from normal volunteers and from patients, to be used in future studies about mutations or polymorphisms of catecholamine-related genes.

Blood Sampling for Neurochemical and Genetic Testing

National Institute of Neurological Disorders and Stroke (NINDS)

Gland and Hormone Related Diseases

Endocrine System Diseases

Levodopa

Dihydroxyphenylalanine

Serotonin

Patients are adults or children of any age with known, sporadic or familial PHEO/PGL

is L 3, 4 dihydroxyphenylalanine (L-DOPA) labeled with the radioactive isotope 18F. In general, PPGLs belong to the group of neuroendocrine tumors. This heterogeneous group of tumors takes up amino acids, transforms them into biogenic amines (dopamine and serotonin) by decarboxylation and stores the amines in vesicles. L DOPA is a precursor of catecholamines (dopamine, norepinephrine and epinephrine). Epinephrine conversion to dopamine is catalyzed by the aromatic amino acid decarboxylase. According to previous and current studies, \[18F\]-DOPA PET is highly sensitive and specific for detection of PHEO/PGL67-69. However, there are only a few reports in the literature using \[18F\]-DOPA as a PET agent and particularly for patients with metastatic PPGLs. PET imaging will be done together with either a CT, an MRI or both modalities.

([18F]-DOPA)

is an imaging agent developed at the NIH, that may improve specificity and sensitivity in the localization of PPGLs. \[18F\]-6F-DA enters cells via the membrane norepinephrine transporter. Once inside cells, \[18F\]-6F-DA is translocated via the vesicular monoamine transporter into storage vesicles, where the radioactivity is concentrated. After injection of \[18F\]-6F-DA, the much faster disappearance of \[18F\]-6F-DA-derived radioactivity from the bloodstream and non-neuronal cells than from chromaffin cells should enable rapid visualization of PPGLs by PET scanning.

([18F]-6F-DA)

Alberta Derkyi, C.R.N.P.

Karel Pacak, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

The goal of this study is to develop better methods of diagnosis, localization, and treatment for pheochromocytomas. These tumors, which usually arise from the adrenal glands, are often difficult to detect with current methods. Pheochromocytomas release chemicals called catecholamines, causing high blood pressure. Undetected, the tumors can lead to severe medical consequences, including stroke, heart attack and sudden death, in situations that would normally pose little or no risk, such as surgery, general anesthesia or childbirth.

Patients with pheochromocytoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Study participants will undergo blood, urine, and imaging tests, described below, to detect pheochromocytoma. If a tumor is found, the patient will be offered surgery. If surgery is not feasible (for example, if there are multiple tumors that cannot be removed), evaluations will continue in follow-up visits. If the tumor cannot be found, the patient will be offered medical treatment and efforts to detect the tumor will continue. Main diagnostic and research tests may include the following:

1. Blood tests - mainly measurements of plasma or urine catecholamines and metanephrines as well as methoxytyramine. If necessary the clonidine suppression test can be carried out.
2. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 123I-MIBG scintigraphy and FDG (positron emission tomography) PET/CT. These scans may be done before and/or after surgical removal of pheochromocytoma.
3. Research PET scanning is done using an injection of radioactive compounds. Patients may undergo 18F-FDOPA, 18F-DA, as well as 68Ga-DOTATATE PET/CT . Each scan takes up to about 2 hours.
4. Genetic testing - A small blood sample is collected for DNA analysis and other analyses.

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare and clinically important chromaffin cell tumors that typically arise from the adrenal gland or from extra-adrenal paraganglia, respectively. The clinical features and consequences of PHEO/PGL result from the release of catecholamines (norepinephrine and/or epinephrine). An undetected PHEO/PGL poses a hazard to patients undergoing surgery, childbirth, or general anesthesia, due to the potential for excess catecholamine secretion, which can result in significant, often catastrophic outcomes. Diagnosing and localizing a PHEO/PGL can be challenging. Plasma and urinary catecholamines as well as their metabolites and radio-iodinated metaiodobenzylguanidine (MIBG) scanning can yield false-positive/negative results in patients harboring the tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) lack sufficient specificity. The molecular mechanisms by which genotypic changes predispose to the development of PHEO/PGL remain unknown - even in patients with identified pathogenic variants. Moreover, in patients with hereditary predispositions, PHEOs/PGLs differ in terms of their growth, malignant potential, catecholamine phenotype, responses to standard screening tests, various imaging modalities and therefore subsequently, different therapeutic options. This protocol focuses on developmental, molecular, genetic, epigenetic, proteomic, metabolomics, immunologic and other types of studies to investigate the bases for predisposition to develop PHEOs/PGLs and for expression of different neurochemical and other phenotypes and malignant potentials including therapeutic responses. Furthermore, this protocol will also use new imaging approaches, for example \[18F\]-6F-dopamine (\[18F\]-6F-DA), and \[18F\]-L-3,4-dihydroxyphenylalanine (\[18F\]-FDOPA) positron emission tomography (PET)/CT, as well as dynamic contrast-enhanced MRI.

Diagnosis of Pheochromocytoma

Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

To study specific genotypes, biochemical and imaging phenotypes of patients with various pheochromocytomas and paragangliomas.To stuty potential treatment options for metastatic pheochromocytoma and paraganglioma using cell cultures, cell lines, animal

To educate health care professionals and patients about pheochromocytoma and paraganglioma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
131MIBG to Treat Malignant Pheochromocytoma	NCT00028106	Pheochromocytom...	[131]I-MIBG 6-[18F]Fluorodo... [123]I-MIBG	18 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Blood Sampling for Neurochemical and Genetic Testing	NCT00001147	Autonomic Nervo... Healthy Hypertension Pheochromocytom...		-	National Institutes of Health Clinical Center (CC)
Diagnosis of Pheochromocytoma	NCT00004847	Pheochromocytom... Endocrine Disea... Endocrine Disea...	([18F]-DOPA) ([18F]-6F-DA)	3 Years - 120 Years	National Institutes of Health Clinical Center (CC)
131MIBG to Treat Malignant Pheochromocytoma	NCT00028106	Pheochromocytom...	[131]I-MIBG 6-[18F]Fluorodo... [123]I-MIBG	18 Years - 70 Years	National Institutes of Health Clinical Center (CC)

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