Hereditary Pheochromocytoma Assessment of Tumour Immunologies

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

Part I:

- Newly diagnosed patients with PPGL or newly diagnosed patients with (metastatic) PPGL recurrence.

- OR patients with mutations which predispose for the development of PPGL.

- Aged > 18 years.

Part II:

- Confirmed PPGL on pathology.

- Aged > 18 years.

Exclusion Criteria:

- Unable to provide informed consent.

- Active inflammatory or infectious comorbidities.

- Other malignancies which are under active treatment (except for basal cell carcinoma, other in situ carcinomas).

- Using medication interfering with the immune system.

- Pregnancy or breastfeeding.

- A self-reported alcohol consumption of >21 units per week

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06444607
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Radboud University Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Margo Dona, PhDHenri Timmers, M.D. PhDRomana Netea-Maier, M.D. PhDMarieke de Laat, M.D. PhD
Principal Investigator Affiliation	Radboud University Medical CenterRadboud University Medical CenterRadboud University Medical CenterRadboud University Medical Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Pheochromocytoma, Paraganglioma

Additional Details

Rationale: Pheochromocytoma and Paraganglioma (PPGL) represent rare, catecholamine-secreting tumours (1). Genetic or sporadic mutations, accounting for approximately 70% of cases, significantly contribute to PPGL development, and are categorized into three clusters based on tumour formation mechanisms (2,3). Current treatment options, particularly for advanced or metastatic disease, are limited (4). Understanding the immune system's role and the impact of genetics on tumour immunology in PPGL could unveil crucial insights for therapeutic advancements. Earlier studies emphasized the immunogenic nature of PPGL, highlighting the tumour microenvironment (TME) and circulatory factors as key components (5-7). However, these studies lack specific examination of genotypes' effect on the immune system. This study aims to address this gap in two parts, particularly focusing on differences between genetic clusters. Objective: To examine the differences in the immune system in PPGL regarding genetics. Part I will examine immune cell composition and response in circulation. Part II will examine immune cell composition in TME. Study design: Part I will be a partly cross-sectional and partly prospective cohort study. Part II will be a histological study of retrospectively and prospectively collected PPGL samples. Study population: Part I will include 80 patients with PPGL, 80 carriers of germline mutations predisposing for PPGL, and 40 sex and age matched healthy volunteers. Part II will include histological samples of 80 patients with hereditary disease and 80 patients with sporadic disease. Main study parameters/endpoints: The main study outcomes are inflammatory molecules and proteins produced by stimulated and unstimulated immune cells from circulation, immune cell composition in histological PPGL samples and in circulation, and their genetic determinants. Secondary outcomes will comprise of transcriptional and epigenetic signature of circulating immune cells, circulating immunomodulating metabolites, trained immunity, and clinical outcomes such as tumour metastasis, survival. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For patients and mutation carriers, there is no direct benefit in participating in this study. However, by participating, they can contribute to the acquisition of scientific knowledge and the development of new therapeutic targets and novel disease management strategies. Such strategies might benefit patients and mutation carriers in the future if they potentially develop advanced disease. There are no risks associated with the study. There are no interventions other than those related to the regular patient care (venipuncture). Thus, this study is considered to impose a low burden on patients.

Arms & Interventions

Arms

: Patients with hereditary PPGL

Blood will be collected prior and after surgery for their pheochromocytoma/paraganglioma (as planned by their treating physician). Blood will also be collected prospectively during regular follow-up appointments after 1 year and after 2 years.

: Patients with sporadic PPGL

: Asymptomatic carriers of germline mutations predisposing for PPGL

Blood will be collected at inclusion, after 1 year and after 2 years.

: Sex and age matched healthy volunteers

Blood material will be obtained from healthy anonymous donors according to the protocol "Donation of blood by healthy volunteers for experimental in-vitro research" (Human Subjects Review Board approval number: NL84281.091.23).

Interventions

Procedure: - Venepuncture

Blood draw in the context of routine patient care, when a venipuncture is already scheduled.

Procedure: - Venepuncture

Volunteering for blood draw.

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Kai Xu, M.D.

[email protected]

+316 42385270

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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