The Epithelioid Hemangioendothelioma Registry of the European Reference Network on Rare Adult Solid Cancers (EURACAN)

NCT06408441 | Recruiting

• 1 other identifier: INT 43-21
• Study Type: observational
• Target: 100
• Locations: 10 countries
• Sites: 21

Brief Summary

Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. The study design is a registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE. The objectives are to improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. It is an hospital-based registry established in centres with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. The data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual. This registry has been developed with the support of EHE Rare Cancer Charity UK, STATER (Grant Agreement number: 947604, HP-PJ-2019) and EURACAN 2022 (Grant Agreement number: 101085486, EU4H-2022-ERN-IBA) European Health and Digital Executive Agency (HaDEA)

Conditions

Epithelioid Hemangioendothelioma; Sarcoma,Soft Tissue

Keywords

rare cancers; soft tissue rare cancer; registry; protocol; ultra rare sarcomas

Outcome Measures

Primary Outcomes (13)

• Male to Female (M/F) ratio

  Difference between the number of males and females

  2 years

• Age average

  The mathematical average age of all the members of a population (i.e. EHE patients)

  2 years

• Comorbidity

  Proportion of patients with Charlson Comorbidity Index (CCI) score mild (CCI scores of 1-2); moderate (CCI scores of 3-4); and severe (CCI scores ≥5)

  2 years

• Performance status

  Proportion of patients by ECOG performance status grade

  2 years

• Cumulative incidence of local recurrence

  proportion of cancer patients who develop a local recurrence over time

  5 years

• Cumulative incidence of distant metastasis

  proportion of cancer patients who develop distant metastases over time

  5 years

• Time to local progression

  Time elapsed from diagnosis to local progression

  5 years

• Time to distant metastases

  Time elapsed from diagnosis to distant metastasis

  5 years

• Overall survival

  The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive

  5 years

• Progression free survival

  The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse

  5 years

• Treatment effectiveness

  Competitive cumulative incidence of local recurrence and distant metastases

  2 years

• Disease free survival

  The length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer.

  5 years

• Description of treatment pattern and quality of care

  Percentage of patients treated according to Consensus paper recommendations

  2 years

Study Arms (3)

unifocal disease

Primary, localized, single lesion

Loco-regional disease

multifocal single-organ involvement

Systemic metastases

multi-organ involvement and/or loco-regional lymph-node involvement

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

It is an hospital based registry thus, hospitals experts in rare cancer. This registry will not select a sample of patients, but it will include every accordant patient present in each facility.

You may qualify if:

• New patients managed by the contributing centers with a pathological EHE diagnosis performed or verified by an expert sarcoma pathologist starting from 1 December 2023 onwards and to be performed within 6 months from the registration
• Molecular confirmation of the diagnosis (WWTR1-CAMTA1 or YAP1-TFE3)
• Adult patients (aged ≥ 18 years)

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (21)

University Hospital Graz

Graz, Graz, 8036, Austria

RECRUITING

Aarhus University Hospital

Aarhus, Aarhus, 8200, Denmark

RECRUITING

Léon Bérard Center

Lyon, Lyon, 69008, France

RECRUITING

Essen University Hospital

Essen, Hesse, 45147, Germany

RECRUITING

Istituto Ortopedico Rizzoli

Bologna, Bologna, 40136, Italy

RECRUITING

Azienda Ospedaliero Universitaria Careggi

Careggi, Firenze, 50134, Italy

RECRUITING

IRCCS Istituto Clinica Humanitas

Rozzano, Milano, 20089, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Milan, 20133, Italy

RECRUITING

Istituto Oncologico Veneto

Padua, Padova, 35128, Italy

RECRUITING

Policlinico Universitario P. Giaccone

Palermo, Palermo, 90127, Italy

RECRUITING

Nuovo Ospedale di Prato "S.Stefano"

Prato, Prato, 59100, Italy

RECRUITING

Università Campus Bio-Medico

Roma, Roma, 00128, Italy

RECRUITING

Istituto Nazionale dei Tumori Regina Elena

Roma, Roma, 00144, Italy

RECRUITING

Azienda Ospedaliera Universitaria San Luigi Gonzaga

Orbassano, Torino, 10043, Italy

RECRUITING

Oslo University hospital Ullevål

Oslo, Oslo County, 0450, Norway

WITHDRAWN

Maria Skłodowska-Curie Institute of Oncology

Warsaw, Warsaw, 00-001, Poland

RECRUITING

Vall d'Hebron University Hospital

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Göteborg, 413 45, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, Stockholm County, 171 76, Sweden

RECRUITING

The Royal Marsden Hospital

London, London, SW3 6JJ, United Kingdom

RECRUITING

Related Publications (14)

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  PMID: 33910263 BACKGROUND

• Blay JY, Piperno-Neumann S, Watson S, Dufresne A, Valentin T, Duffaud F, Toulmonde M, Italiano A, Bertucci F, Tlemsani C, Firmin N, Bompas E, Perrin C, Ropars M, Saada-Bouzid E, Dubray-Longeras P, Hervieu A, Lebbe C, Gantzer J, Chaigneau L, Fiorenza F, Rios M, Isambert N, Soibinet P, Boudou-Roquette P, Verret B, Ferron G, Ryckewaert T, Lebellec L, Brahmi M, Gouin F, Meeus P, Vaz G, Le Loarer F, Karanian M, De Pinieux G, Ducimetiere F, Chemin C, Morelle M, Le Cesne A, Penel N; NETSARC/REPPS/RESOS and French Sarcoma Group-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO) networks. Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years. Eur J Cancer. 2023 Oct;192:113262. doi: 10.1016/j.ejca.2023.113262. Epub 2023 Jul 29.

  PMID: 37625241 BACKGROUND

• Stacchiotti S, Miah AB, Frezza AM, Messiou C, Morosi C, Caraceni A, Antonescu CR, Bajpai J, Baldini E, Bauer S, Biagini R, Bielack S, Blay JY, Bonvalot S, Boukovinas I, Bovee JVMG, Boye K, Brodowicz T, Callegaro D, De Alava E, Deoras-Sutliff M, Dufresne A, Eriksson M, Errani C, Fedenko A, Ferraresi V, Ferrari A, Fletcher CDM, Garcia Del Muro X, Gelderblom H, Gladdy RA, Gouin F, Grignani G, Gutkovich J, Haas R, Hindi N, Hohenberger P, Huang P, Joensuu H, Jones RL, Jungels C, Kasper B, Kawai A, Le Cesne A, Le Grange F, Leithner A, Leonard H, Lopez Pousa A, Martin Broto J, Merimsky O, Merriam P, Miceli R, Mir O, Molinari M, Montemurro M, Oldani G, Palmerini E, Pantaleo MA, Patel S, Piperno-Neumann S, Raut CP, Ravi V, Razak ARA, Reichardt P, Rubin BP, Rutkowski P, Safwat AA, Sangalli C, Sapisochin G, Sbaraglia M, Scheipl S, Schoffski P, Strauss D, Strauss SJ, Sundby Hall K, Tap WD, Trama A, Tweddle A, van der Graaf WTA, Van De Sande MAJ, Van Houdt W, van Oortmerssen G, Wagner AJ, Wartenberg M, Wood J, Zaffaroni N, Zimmermann C, Casali PG, Dei Tos AP, Gronchi A. Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts. ESMO Open. 2021 Jun;6(3):100170. doi: 10.1016/j.esmoop.2021.100170. Epub 2021 Jun 2.

  PMID: 34090171 BACKGROUND

• Amin RM, Hiroshima K, Kokubo T, Nishikawa M, Narita M, Kuroki M, Nakatani Y. Risk factors and independent predictors of survival in patients with pulmonary epithelioid haemangioendothelioma. Review of the literature and a case report. Respirology. 2006 Nov;11(6):818-25. doi: 10.1111/j.1440-1843.2006.00923.x.

  PMID: 17052315 BACKGROUND

• Stacchiotti S, Simeone N, Lo Vullo S, Baldi GG, Brunello A, Vincenzi B, Palassini E, Dagrada G, Collini P, Morosi C, Greco FG, Sbaraglia M, Dei Tos AP, Mariani L, Frezza AM, Casali PG. Activity of sirolimus in patients with progressive epithelioid hemangioendothelioma: A case-series analysis within the Italian Rare Cancer Network. Cancer. 2021 Feb 15;127(4):569-576. doi: 10.1002/cncr.33247. Epub 2020 Oct 27.

  PMID: 33107985 BACKGROUND

• Frezza AM, Napolitano A, Miceli R, Badalamenti G, Brunello A, Buonomenna C, Casali PG, Caraceni A, Grignani G, Gronchi A, Infante G, Morosi C, Saita L, Simeone N, Zaffaroni N, Vincenzi B, Stacchiotti S. Clinical prognostic factors in advanced epithelioid haemangioendothelioma: a retrospective case series analysis within the Italian Rare Cancers Network. ESMO Open. 2021 Apr;6(2):100083. doi: 10.1016/j.esmoop.2021.100083. Epub 2021 Mar 10.

  PMID: 33714008 BACKGROUND

• Frezza AM, Ravi V, Lo Vullo S, Vincenzi B, Tolomeo F, Chen TW, Teterycz P, Baldi GG, Italiano A, Penel N, Brunello A, Duffaud F, Hindi N, Iwata S, Smrke A, Fedenko A, Gelderblom H, Van Der Graaf W, Vozy A, Connolly E, Grassi M, Benjamin RS, Broto JM, Grignani G, Jones RL, Kawai A, Tysarowski A, Mariani L, Casali PG, Stacchiotti S. Systemic therapies in advanced epithelioid haemangioendothelioma: A retrospective international case series from the World Sarcoma Network and a review of literature. Cancer Med. 2021 Apr;10(8):2645-2659. doi: 10.1002/cam4.3807. Epub 2021 Mar 13.

  PMID: 33713582 BACKGROUND

• Engel ER, Cournoyer E, Adams DM, Stapleton S. A Retrospective Review of the Use of Sirolimus for Pediatric Patients With Epithelioid Hemangioendothelioma. J Pediatr Hematol Oncol. 2020 Nov;42(8):e826-e829. doi: 10.1097/MPH.0000000000001643.

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• Shibayama T, Makise N, Motoi T, Mori T, Hiraoka N, Yonemori K, Watanabe SI, Esaki M, Morizane C, Okuma T, Kawai A, Ushiku T, Yatabe Y, Yoshida A. Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases: A Proposal of Risk Stratification and Identification of a Synaptophysin-positive Aggressive Subset. Am J Surg Pathol. 2021 May 1;45(5):616-626. doi: 10.1097/PAS.0000000000001660.

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Biospecimen

Retention: NONE RETAINED

Tumour and healthy biological samples (paraffin-embedded or fresh tissue, blood) previously collected in the course of routine health care

MeSH Terms

Conditions

Hemangioendothelioma, Epithelioid; Sarcoma

Condition Hierarchy (Ancestors)

Hemangioendothelioma; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective and Soft Tissue

Central Study Contacts

Annalisa Trama, MD

CONTACT

02 2390 3535; annalisa.trama@istitutotumori.mi.it

Melissa Gil Sanjines

CONTACT

02 2390 3564; melissa.gilsanjines@istitutotumori.mi.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 3, 2024
• First Posted: May 10, 2024
• Study Start: December 1, 2023
• Primary Completion (Estimated): December 1, 2033
• Study Completion (Estimated): December 1, 2033
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: 5 years
• Access Criteria: 1. data remain the contributing Health Care Providers (HCP) 2. each HCP is free to access and use its own data for research 3. each contributing HCP and third parties can request access to the database following the rules including in the governance

Locations

SE (2); DE (1); FR (1); PL (1); GB (1); AU (1); NO (1); IT (10); DK (1); ES (2)