Clinical Research Directory

Prospective Cohort Study of Pheochromocytoma/Paraganglioma

The study will enroll patients scheduled for PPGL removal surgery at Peking Union Medical College Hospital. Before surgery, researchers will use a 6-variable model to predict the patient's risk of experiencing severe blood pressure swings during the operation. During surgery, a real-time early warning tool will be tested for its ability to accurately predict blood pressure changes 60 seconds in advance. The study will also explore the value of continuous glucose monitoring (CGM) in understanding blood pressure fluctuations and evaluate the performance of an artificial intelligence (AI) agent for preoperative anesthesia assessment, comparing its accuracy, consistency, and efficiency against that of human anesthesiologists. Participation involves no changes to the patient's standard surgical or medical care. It includes collecting clinical data, wearing a CGM sensor from the day before to the day after surgery, and having the preoperative assessment performed by both the AI agent and anesthesiologists.

Iodine I 131 Metaiodobenzylguanidine in Treating Patients With Recurrent, Progressive, or Refractory Neuroblastoma or Malignant Pheochromocytoma or Paraganglioma

The purpose of this research study is to find how active and safe 131 I-MIBG is in patients with resistant neuroblastoma, malignant pheochromocytoma and malignant paraganglioma.

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

Background: Pheochromocytoma and paraganglioma are rare tumors. They usually form inside and near the adrenal gland or in the neck region. Not all these tumors can be removed with surgery, and there are no good treatments if the disease has spread. Researchers think a new drug may be able to help. Objective: To learn the safety and tolerability of Lu-177-DOTATATE. Also, to see if it improves the length of time it takes for the cancer to return. Eligibility: Adults who have an inoperable tumor of the study cancer that can be detected with Ga-68-DOTATATE PET/CT imaging Design: Participants will be screened with a medical history, physical exam, and blood tests. Eligible participants will be admitted to the NIH Clinical Center. Participants will get the study drug in an intravenous infusion. They will get 4 doses, given about 8 weeks apart. Between 4 and 24 hours after each study drug dose, participants will have scans taken. They will lie on their back on a scanner table. Participants will have vital signs taken. They will give blood and urine samples. During the study, participants will have other scans taken. Some scans will use a radioactive tracer. Participants will complete quality of life questionnaires. Participants will be contacted by phone 1-3 days after they leave the Clinical Center. They will then be followed every 3 to 6 months for 3 years or until their disease gets worse.

Diagnosis of Pheochromocytoma

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.

Gene Modified Immune Cells After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors

This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.

Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy

Background: Gastrointestinal neuroendocrine tumors (GI NET) are a type of cancer that affects the stomach and intestines; pheochromocytoma/paragangliomas (PPGL) are tumors that grow in or near the adrenal glands. Both of these types of tumor have high levels of a protein called somatostatin receptors (SSTR) on their surfaces. Researchers want to test a treatment that targets SSTR. Objective: To test a drug (\[212Pb\]VMT-alpha-NET) in people with GI NET or PPGL. The drug has 2 components: a protein to bind to SSTR and a radioactive agent to kill the cancer cells. Eligibility: Adults aged 18 years or older with GI NET or PPGL tumors that have spread and cannot be removed with surgery. Design: Participants will be screened. They will have a physical exam, with imaging scans, blood tests, and tests of their heart function. \[212Pb\]VMT-alpha-NET is given through a tube attached to a needle inserted into a vein (infusion). Treatment will be given in four 8 week cycles. Participants will receive the drug on the first day of each cycle. They will remain in the clinic at least 4 hours after each infusion and may need to stay in the hospital for up to 48 hour for monitoring and testing. They will have blood tests every week of each cycle. Some participants will also get a related study drug (\[203Pb\]VMT-alpha-NET). They will receive this drug a few days before the first 2 cycles. At 4, 24, and 48 hours after each infusion, they will have whole body scans. These scans will show where the study drug went in their body. Follow-up visits will continue for 10 years....

LAnreotide in Metastatic Pheochromocytoma / PARAganglioma (LAMPARA)

The objectives of this study are: * To assess the efficacy of lanreotide given every 4 weeks in participants with advanced or metastatic paraganglioma/ pheochromocytoma. * To assess the toxicity and safety of lanreotide in participants with advanced or metastatic paraganglioma/ pheochromocytoma. * To document the effects of lanreotide on markers of biochemical activity in participants with advanced or metastatic paraganglioma/ pheochromocytoma. Primary endpoints: • Assess efficacy by estimating the tumor growth rate while a patient is enrolled on study and comparing the growth rates on lanreotide to the pre-enrolment growth rate. Secondary endpoints include measurement of: * Overall survival (OS) * Progression-free survival (PFS) * Overall response rate (ORR) according to RECIST defined as partial response (PR) + complete response (CR) * Magnitude of reduction in levels of 24-hour urinary metanephrines, catecholamines and magnitude of reduction in serum chromogranin A, evaluated every two months while enrolled on study.

Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Pheochromocytoma/Paraganglioma

Primary Objective: To determine the response rate (RR) of metastatic or locally advanced pheochromocytoma/paraganglioma to axitinib administered daily. Secondary Objectives: * Determine the progression-free survival. * In an exploratory manner examine the extent of activation of the VEGFR pathway in pheochromocytoma/paraganglioma using a semi-quantitative immunohistochemistry assay and examine the relationship with response to therapy. * Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline DNA examination.

In Vivo PARP-1 Expression With 18F-FluorThanatrace PET/CT in Patients With Pheochromocytoma and Paraganglioma

This study will enroll up to 30 evaluable patients with pheochromocytoma or paraganglioma who are undergoing surgical or systemic treatment. A pre-treatment 18F-FluorThanatrace (\[18F\]FTT) positron emission tomography/computed tomography (PET/CT) scan will be done prior to surgery or systemic therapy. PET/CT imaging will be used to evaluate PARP-1 expression in sites of pheochromocytoma or paraganglioma using the investigational radiotracer \[18F\]FTT. This is an observational study in that \[18F\]FTT PET/CT will not be used to direct treatment decisions. While patients and referring physicians will not be blinded to the \[18F\]FTT PET/CT results, treatment decisions will be made by the treating physicians based upon clinical criteria.

Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs

This is a multicenter, open-label, single-arm study to evaluate the safety and dosimetry of Lutathera in adolescent patients 12 to \<18 years old with somatostatin receptor positive GEP-NETs and PPGLs. The study will enroll at least 8 patients in the GEP-NET cohort and as many adolescents with PPGL as possible in the exploratory PPGL cohort.

Institutional Registry of Rare Diseases

The goal of this observational study is to create a single macro registry system with data collection on common clinical features, grouping the different rare diseases (RD). Moreover, the specific goals are to generate an alert system for possible cases of RD with data from the electronic medical record, to describe the occurrence of RD in the evaluated population, to characterize the population, to describe patterns of diagnosis and treatment of RD present at the time, and to explore patient-reported outcomes.

18F-Fluorodopamine PET Studies of Neuroblastoma and Pheochromocytoma

PET (positron emission tomography) scans combined with a radioactive tracer will be used to identify and analyze tumors. Currently, the most common tracer used to analyze neuroblastoma tumors is called 123I-mIBG. However, the picture it provides is not always clear enough to see the very small areas of the disease. 18F-DA (18F-fluorodopamine) has been shown to be safe and more effective than 123I-mIBG in analyzing the tumor pheochromocytoma, which is closely related to neuroblastoma. With this research study, the investigators plan to meet the following goals: * Investigate to see if 18F-DA is safe to administer to pediatric patients with known or suspected neuroblastoma or pheochromocytoma * Examine where in the body 18F-DA goes. * Obtain information comparing 18F-DA to 123I-mIBG to see if 18F-DA could replace 123I-mIBG in the future. About 20 people, with known or suspected neuroblastoma or pheochromocytoma, will take part in this Pilot study at St. Jude.

Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Neuroendocrine Tumors

This study is Phase I/IIa First-in-Human Study of \[212Pb\]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors

Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions

Pheochromocytomas and paragangliomas are neural crest-derived tumors of the nervous system that are often inherited and genetically heterogeneous. Genetic screening is recommended for patients and their relatives, and can guide clinical decisions. However, a mutation is not found in all cases. The aims of this proposal are to: 1) to map gene(s) involved in pheochromocytoma, and 2) identify genotype-phenotype correlations in patients with pheochromocytoma/paraganglioma of various genetic origins.

Cardiovascular Complications After Adrenalectomy for Pheochromocytoma and Non-secreting Tumors

Pheochromocytoma is an adrenomedullary chromaffin cell tumour that releases catecholamines. Adverse cardiovascular events are considered the main cause of morbidity and mortality in patients with pheochromocytoma. Consequently, preoperative medical preparations using alpha-blockers or other antihypertensive drugs and the control of hemodynamic instability during adrenalectomy for pheochromocytoma are recommended by guidelines to prevent vasoconstriction, perioperative cardiovascular complications, and the risk of death. However, the definition of a catecholamine-induced hypertensive crisis in patients with pheochromocytoma has only recently been validated by an international consortium as the occurrence of systolic/diastolic blood pressure \>180/120 mmHg1. Limitations of published studies include small sample sizes, and single institution analysis. Some studies have reported substantial variability in the management of pheochromocytomas, with the use of routine preoperative medical preparation varying from 49% to 100%, whereas others have questioned the utility of this preparation for postoperative cardiovascular complications. The aim of this study was to evaluate pan-European practices in terms of specific preoperative medical preparation before surgery and to identify risk factors for postoperative cardiovascular complications 30 days after adrenalectomy for pheochromocytoma and non-secreting tumors (indication for surgery = " excluding malignancy "). The EUROCRINE® registry offers a valuable opportunity to assess clinical practices for preoperative medical preparation and the morbidity linked to adrenalectomy for pheochromocytoma and non-secreting tumors. This prospective study aims to refine surgical protocols and inform updates to existing guidelines, thereby advancing the management of adrenalectomy for pheochromocytoma.

Clinical Application of Somatostatin Receptor and Norepinephrine Transporter Targeted Imaging for Diagnosis and Staging of Neuroblastoma and Pheochromocytoma/Paraganglioma

The goal of this clinical trial is to evaluate the diagnostic efficacy of somatostatin receptor and norepinephrine transporter targeted imaging (including 18F-MFBG, 123I-MIBG, 131I-MIBG, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE, 68Ga-DOTA-TOC, and other radiolabeled somatostatin analogues) in the diagnosis and staging of neuroblastoma and pheochromocytoma/paraganglioma patients aged 1-70 years. The main questions it aims to answer are: Can molecular targeted imaging using various norepinephrine transporter tracers (18F-MFBG, 123I/131I-MIBG) and somatostatin receptor tracers (68Ga-DOTA-peptides series) accurately detect primary tumors and metastatic lesions in neuroblastoma/pheochromocytoma patients? What is the comparative diagnostic performance (sensitivity, specificity, accuracy) of different molecular imaging techniques compared to histopathological diagnosis as the gold standard? Researchers will compare the imaging findings from multiple tracer types with surgical pathology results to assess diagnostic accuracy and clinical staging precision. Participants will: * Undergo screening assessments including medical history, physical examination, and laboratory tests * Receive intravenous injection of selected tracers (18F-MFBG, 68Ga-DOTA-NOC/TATE, or other appropriate agents) at standardized doses followed by PET-CT/MRI imaging at optimal time points * Undergo histopathological examination within 2 months post-imaging * Complete safety follow-up for 6 months to monitor for any adverse reactions to the imaging agents

Adrenal Tumors - Pathogenesis and Therapy

The pathogenesis of adrenal tumors is still not fully elucidated and the treatment options for malignant tumors are poor. The current study investigates different aspects of the pathogenesis of adrenal tumors and evaluates different therapeutic options in patients with adrenocortical carcinoma.

18F-mFBG PET Imaging in the Evaluation of Pheochromocytoma

The aim of this study is to evaluate the diagnostic performance and tumor burden of 18F-metafluorobenzylguanidine (18F-MFBG) positron emission tomography (PET) in patients with pheochromocytoma.

Using the EHR to Advance Genomic Medicine Across a Diverse Health System

Given the expansion of indications for genetic testing and our understanding of conditions for which the results change medical management, it is imperative to consider novel ways to deliver care beyond the traditional genetic counseling visit, which are both amenable to large-scale implementation and sustainable. The investigators propose an entirely new approach for the implementation of genomic medicine, supported by the leadership of Penn Medicine, investigating the use of non-geneticist clinician and patient nudges in the delivery of genomic medicine through a pragmatic randomized clinical trial, addressing NHGRI priorities. Our application is highly conceptually and technically innovative, building upon expertise and infrastructure already in place. Innovative qualities of our proposal include: 1) Cutting edge EHR infrastructure already built to support genomic medicine (e.g., partnering with multiple commercial genetic testing laboratories for direct test ordering and results reporting in the EHR); 2) Automated EHR-based direct ordering or referring by specialist clinicians (i.e., use of replicable modules that enable specialist clinicians to order genetic testing through Epic Smartsets, including all needed components, such as populated gene lists, smartphrases, genetic testing, informational websites and acknowledgement e-forms for patient signature); 3) EHR algorithms for accurate patient identification (i.e., electronic phenotype algorithms to identify eligible patients, none of which currently have phenotype algorithms present in PheKB; 4) Behavioral economics-informed implementation science methods: This trial will be the first to evaluate implementation strategies informed by behavioral economics, directed at clinicians and/or patients, for increasing the use of genetic testing; further it will be the first study in this area to test two forms of defaults as a potential local adaptation to facilitate implementation (ordering vs. referring); and 5) Dissemination: In addition to standard dissemination modalities,PheKB95, GitHub and Epic Community Library, the investigators propose to disseminate via AnVIL (NHGRI's Genomic Data Science Analysis, Visualization, and Informatics Lab-Space). Our results will represent an entirely new paradigm for the provision of genomic medicine for patients in whom the results of genetic testing change medical management.

DOTATOC PET/CT for Imaging NET Patients

Neuroendocrine tumours (NETs) are generally slow growing, but some can be aggressive and resistant to treatment. Compared to healthy cells, the surface of these tumor cells has a greater number of special molecules called somatostatin receptors (SSTR). Somatostatin receptor scintigraphy and conventional imaging are used to detect NETs. This study proposes 68Gallium(68Ga)-DOTATOC positron emission tomography/computed tomography (PET/CT) is superior to current imaging techniques. The goal is to evaluate the safety and sensitivity of 68Ga-DOTATOC PET/CT at detecting NETs and other tumors with over-expression of somatostatin receptors.

The Effect and Safety of Omitting Preoperative Alpha-adrenergic Blockade for Normotensive Pheochromocytoma

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors originating from catecholamine producing chromaffin cells in the adrenal medulla and extra-adrenal paraganglia. The overall age-standardized incidence rate is 0.18 per 100,000 person-years in Korea. The definitive treatment of PPGL is surgical excision of tumor. However, surgery is associated with a high risk of perioperative hemodynamic instability (HI). To avoid perioperative HI in patients diagnosed with PPGL, preoperative management including routine use of alpha blockade and volume expansion has been advocated by several guidelines. While unstable hypertension and tachycardia should be controlled in patients with PPGL, there is controversial that all patients diagnosed with PPGL should undergo preoperative pharmacological treatment, especially alpha blockade. The most important risk of preoperative alpha blockade use is perioperative hypotension. A recent study reported that patients diagnosed with PPGL postoperatively may have no further higher risk of intraoperative hypertension than those diagnosed preoperatively despite insufficient preoperatively management of PPGL. Therefore, it is a very important to study the relationship between HI and preoperative alpha blockade in normotensive patients diagnosed with PPGL. The aim this study is to analyze the effect and safety of omitting preoperative alpha-adrenergic blockade for normotensive pheochromocytoma through a prospective randomized controlled trial. The patients is divided into two groups. The patients in control group take a phenoxybenzamine at least 2 to 5 weeks before surgery. The patients in case group do not take a phenoxybenzamine. Primary outcome is to evaluate the percentage of time during surgery with systolic blood pressure more than 160mmHg or average blood pressure less than 60mmHg. And secondary outcomes are to evaluate hemodynamic instability in preoperative ward and postoperative ward.

Anlotinib Combined With Benmelstobart for Advanced Pheochromocytoma

There is currently no standard first-line treatment for stage PPGL, and the 5-year survival rate of patients with advanced pheochromocytoma/paraganglioma (PPGL) is low, ranging from 30% to 60%. At present, several domestic teams have carried out clinical studies on the treatment of advanced PPGL with good efficacy. In the early stage, our center used anrotinib to treat advanced PPGL, and the overall effective rate reached 44%. In the early stage, our team used anrotinib combined with PD-1 monoclonal antibody to treat advanced PPGL patients. The effective rate reached 66% (2/3). Therefore, the investigators plan to further conduct prospective studies to explore the efficacy and safety of anlotinib combined with PD-1 monoclonal antibody in the treatment of advanced PPGL, so as to bring benefits to patients with advanced PPGL.

Hereditary Pheochromocytoma Assessment of Tumour Immunologies

In this study, the investigators are examining the role of the immune system in pheochromocytoma and paraganglioma. The investigators aim to examine the differences in the immune system between people who have these tumors with and without a hereditary predisposition. The investigators also want to see how the immune system changes during the development of the tumor in people with a hereditary predisposition. Finally, the investigators will compare the data with a control group of people without these tumors. Ultimately, the investigators hope that the results will contribute to the discovery of new immune system-targeted medications for pheochromocytoma and paraganglioma.

Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined with the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).

Study in children and adolescents of 177Lu DOTATATE (Lutathera®) combined with the PARP inhibitor olaparib for treatment of recurrent or relapsed solid tumours expressing somatostatin receptors (SSTR) (LuPARPed)