Hereditary Pheochromocytoma Assessment of Tumour Immunologies

NCT06444607 | Recruiting DMC

• 1 other identifier: 115703
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pheochromocytoma; Paraganglioma

Keywords

Pheochromocytoma; Paraganglioma; Tumor microenvironment; Innate immunity

Outcome Measures

Primary Outcomes (2)

• Immune cell response in circulation, both after stimulation and in an unstimulated state, measured as the concentration of inflammatory molecules and proteins.

  e.g. cytokines

  Before surgery, 6 weeks after surgery, after 1 year, after 2 years.

• Immune cell composition in histological PPGL specimens and in circulation.

  Before surgery, 6 weeks after surgery, after 1 year, after 2 years. Histological specimens will only be obtained during surgery.

Secondary Outcomes (6)

• Transcriptional and epigenetic signature of circulating immune cells.

  Before surgery, 6 weeks after surgery, after 1 year, after 2 years.

• Concentration of immunomodulating metabolites in circulation.

  Before surgery, 6 weeks after surgery, after 1 year, after 2 years.

• Trained immunity assessment of circulating immune cells.

  Before surgery, 6 weeks after surgery, after 1 year, after 2 years.

• Tumour recurrence rate

  After 1 year, after 2 years.

• Metastasis rate

  Before surgery, after 1 year, after 2 years.

Study Arms (4)

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.

Procedure: Venepuncture

Patients with sporadic 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.

Procedure: Venepuncture

Asymptomatic carriers of germline mutations predisposing for PPGL

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

Procedure: Venepuncture

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).

Procedure: Venepuncture

Interventions

Venepuncture PROCEDURE

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

Asymptomatic carriers of germline mutations predisposing for PPGL; Patients with hereditary PPGL; Patients with sporadic PPGL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

For part I, the study population will consist of patients who are presenting or are currently under follow-up at the Radboudumc endocrinology department for their PPGL. Eigthy patients will be included with hereditary or sporadic cases of PPGL and an equal number of asymptomatic carriers. The healthy control group will consist of 40 age and sex matched healthy volunteers. Part II will include histological samples of 160 patients with PPGL, of which 80 hereditary and 80 sporadic. A large part of the population will overlap between part I and part II, since almost all patients with PPGL undergo surgery for their tumour. These samples will partly be retrospectively collected from the Radboudumc Urology Biobank, where biomaterials from previously treated patients with PPGLs are kept and stored or future scientific research (Human Subjects Review Board approval number: CWOM-9803-0060). The remaining samples will be collected prospectively from patients undergoing surgery for their PPGL.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

RECRUITING

Related Publications (7)

• Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 2005 Aug 20-26;366(9486):665-75. doi: 10.1016/S0140-6736(05)67139-5.

  PMID: 16112304 BACKGROUND

• Cascon A, Calsina B, Monteagudo M, Mellid S, Diaz-Talavera A, Curras-Freixes M, Robledo M. Genetic bases of pheochromocytoma and paraganglioma. J Mol Endocrinol. 2023 Jan 24;70(3):e220167. doi: 10.1530/JME-22-0167. Print 2023 Apr 1.

  PMID: 36520714 BACKGROUND

• Jhawar S, Arakawa Y, Kumar S, Varghese D, Kim YS, Roper N, Elloumi F, Pommier Y, Pacak K, Del Rivero J. New Insights on the Genetics of Pheochromocytoma and Paraganglioma and Its Clinical Implications. Cancers (Basel). 2022 Jan 25;14(3):594. doi: 10.3390/cancers14030594.

  PMID: 35158861 BACKGROUND

• Nolting S, Bechmann N, Taieb D, Beuschlein F, Fassnacht M, Kroiss M, Eisenhofer G, Grossman A, Pacak K. Personalized Management of Pheochromocytoma and Paraganglioma. Endocr Rev. 2022 Mar 9;43(2):199-239. doi: 10.1210/endrev/bnab019.

  PMID: 34147030 BACKGROUND

• Tufton N, Hearnden RJ, Berney DM, Drake WM, Parvanta L, Chapple JP, Akker SA. The immune cell infiltrate in the tumour microenvironment of phaeochromocytomas and paragangliomas. Endocr Relat Cancer. 2022 Sep 19;29(11):589-598. doi: 10.1530/ERC-22-0020. Print 2022 Nov 1.

  PMID: 35975974 BACKGROUND

• Gao X, Yamazaki Y, Pecori A, Tezuka Y, Ono Y, Omata K, Morimoto R, Nakamura Y, Satoh F, Sasano H. Histopathological Analysis of Tumor Microenvironment and Angiogenesis in Pheochromocytoma. Front Endocrinol (Lausanne). 2020 Nov 10;11:587779. doi: 10.3389/fendo.2020.587779. eCollection 2020.

  PMID: 33244312 BACKGROUND

• van der Heijden CDCC, Groh L, Keating ST, Kaffa C, Noz MP, Kersten S, van Herwaarden AE, Hoischen A, Joosten LAB, Timmers HJLM, Netea MG, Riksen NP. Catecholamines Induce Trained Immunity in Monocytes In Vitro and In Vivo. Circ Res. 2020 Jul 3;127(2):269-283. doi: 10.1161/CIRCRESAHA.119.315800. Epub 2020 Apr 3.

  PMID: 32241223 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, and white blood cells from participating patients, obtained from whole blood during routine care. Histological samples from PPGL tissue after planned surgery.

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Margo Dona, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Henri Timmers, M.D. PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Romana Netea-Maier, M.D. PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Marieke de Laat, M.D. PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kai Xu, M.D.

CONTACT

+316 42385270; kai.xu@radboudumc.nl

Marieke de Laat, M.D. PhD

CONTACT

+3124 361 4599; marieke.delaat@radboudumc.nl

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: June 5, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: November 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: One year after completion of the study.

Locations

NL (1)