Ignite Creation Date:
2024-05-11 @ 8:30 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06408441
Status:
RECRUITING
Last Update Posted:
2024-05-10
First Post:
2024-04-03
Brief Title:
The Epithelioid Hemangioendothelioma Registry of the European Reference Network on Rare Adult Solid Cancers EURACAN
Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Organization:
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Study Overview
Official Title:
The Observational EURACAN Prospective Clinical Registry Dedicated to Epithelioid Hemangioendothelioma the Protocol of an International and Collaborative Effort on an Ultra-rare Entity
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EHE
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 Coxs 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 patients 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
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 Coxs 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 patients 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
Detailed Description:
Given its incidence of 0038100 000year EHE is an ultra-rare sarcoma with distinctive well-defined pathological molecular and clinical features It belongs to the group of vascular sarcomas and is characterized by WWTR1-CAMTA1 90 or YAP1-TFE3 10 gene fusions which represents today a hallmark for diagnosis EHE potentially arises everywhere in the body and shows a high tendency toward metastatic spread especially in the lung liver and bone The onset is characterized by different presentations including a unifocal lesion usually in the soft tissues locoregional metastases multiple lesions in a single organ or in a single anatomic compartment and systemic metastases multi-organ involvement Also the biological behavior of the disease is unique in sarcomas and variable with spontaneous regressions reported patients with untreated stable disease overtime slowly progressive variants and highly aggressive and rapidly fatal cases Today the relative incidence of the different presentations is undefined the natural history of the different subtypes is poorly understood and reliable clinical or biological prognostic factors are lacking Retrospective data suggest that patients with EHE presenting or developing during their course serosal involvement and or effusion systemic associated symptoms and anemia have a worse prognosis but a prospective validation of this observation is lacking In terms of management surgery is the treatment of choice for localized disease with an excellent outcome expected cure rate of 70-80 and no proven role for local or systemic adjuvant therapies For patients with advanced asymptomatic disease active surveillance is often the upfront choice in order to minimize the risk of overtreatment Systemic therapies are usually considered for patients with progressive or symptomatic disease although a standard medical approach is currently not established Unfortunately conventional chemotherapy including anthracycline-based regimens widely regarded as the mainstay in the treatment of advanced soft tissue sarcomas showed marginal activity in EHE The use of potentially active compounds such as m-TOR inhibitors which proved the highest activity in EHE and could therefore represent the preferred option is limited by regulatory constraints as they are not currently labeled in Europe for this indication Given the degree of uncertainty on EHE management a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology ESMO involving 80 multidisciplinary worldwide experts together with a patient representative with the aim of defining by consensus evidence-based best practices for the optimal approach to primary and metastatic EHE
Since the number of patients is inherently low at the hospital level the only way to increase knowledge about EHE and improve the diagnosis treatment and prognosis of this complex and heterogeneous disease is to harmonize and combine real-world data from sarcoma expert centres by leveraging a wide international joined effort In this context a unique opportunity is provided by the European Reference Networks ERNs virtual network established by the EU commission aiming to tackle rare conditions including cancers Among the three ERNs dedicated to cancer EURACAN httpseuracaneu is the one focusing on the 10 families of rare adult solid cancers RACs including soft tissue sarcomas bone sarcomas and gastrointestinal stromal tumour Fostering academic research and promote epidemiological surveillance in rare cancers through setting up of shared registries is recognize as one of ERNs priorities Within the sarcoma domain taking into account the challenges described above priority was given to ultra-rare sarcoma and thanks to the strong connection motivation and support provided by EHE Rare Cancer Charity UK it was decided to start from EHE We believe that in this context the collection of high-quality data by clinical registries will be crucial to improve the understanding of EHE natural history validate and identify new prognostic factors clarify the activity and efficacy of currently available treatment options and eventually provide and external control which might serve as a benchmark for the development of new drugs and support discussion with regulatory authorities
The EURACAN EHE registry is a prospective clinical registry that will collect data from all new patients receiving a pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023 To this aim an EHE-focused clinical record form CRF was developed through the Research Electronic Data Capture REDCap and designed to capture the specific features of this disease
For each patient data collection will include
1 A common baseline including full details on demographic comorbidities special focus on immune-mediated and gynecological diseases concomitant medications physical examination systemic symptoms at presentation tumour-related pain assessment blood tests pathology and molecular features on the diagnostic specimen EHE extension at baseline unifocal disease loco-regional disease systemic metastases
2 Depending on the disease extent detail on staging modalities primary site and size extension of metastatic disease organs involved number of lesions presence and characterization of serosal involvement and effusion treatment surgery radiation therapy medical therapies isolated limb perfusion other locoregional techniques
Although the EHE registry per se does not foresee any collection of pathological samples and or imaging the availability for each enrolled patient of pathological samples massive parallel sequencing data and imaging at the contributing institution will be captured by the CRF in order to facilitate patients identification for future dedicated studies which will imply the use of these data
Given the peculiar biological EHE behavior in absence of any event a mandatory 6-monthly update will be required at all contributing centers In the mandatory 6-monthly update information from the last visit will be recorded regarding physical examination time interval of development of systemic symptoms assessment of tumor-related pain blood tests update on ongoing treatment active surveillance including modalities and timing of radiological monitoring and radiological response
All events will be recorded at the time of the occurrence for unifocal disease local recurrence and metastatic progression for locoregional and metastatic disease systemic progression For every event information will be recorded on physical examination time interval of development of systemic symptoms assessment of tumor-related pain assessment blood tests hemoglobin and fibrinogen radiological modalities detecting progression extent of progression by RECIST 11 and not serosal involvement and or effusion update on ongoing treatment active surveillance
Patient status alive with no evidence of disease alive with disease dead and last follow up will be updated at any data entry
The registry and therefore the electronic CRF have been shaped starting from what have been agreed and reported in the EHE consensus paper from the sarcoma community of experts published in 2021 A registry kick-off meeting was held in Milan the 15th September 2023 involving the EHE prospective clinical registry coordination team all the contributing centers and patients associations EHE Rare Cancer Charity UK EHE Italia and EHE US to present the registry and share common clinical practice guidelines derived from the consensus paper to be followed for the patients with EHE included in the registry
The launch of the EHE prospective clinical registry was shared with all the reference institutions belonging as full members or associated partners to EURACAN sarcoma domain 63 institutions across Europe
The project was also opened to EU institutions not belonging to EURACAN and extra-EU institutions In this case in order to ensure an adequate degree of expertise in the disease the institutions interested in joining the registry were asked to provide the number of new EHE cases molecularly confirmed seen each year over 3 years 2020-2021-2022 and a threshold of at least 20 of EHE national incident cases was selected for participation
As a result of this process 21 institutions joined the registry in September 2023 17 of which belonging to EURACAN from 10 countries
The registry is federated thus data are stored by the health care providers contributing to the registry At the local level data are pseudonymised
Statistical analyses will be performed based on a study protocol Queries will be developed in collaboration with clinical experts to interrogate the EURACAN EHE registry to generate the descriptive statistics and relevant information needed to plan the analyses envisaged by the study protocol
Data quality checks aim to assess whether data values are present if they adhere to specific standard and if they are believable in terms of
Conformance the data should be recorded in agreement with the correct formats eg range of values date formats
Completeness the data should not have missing values or data records
Plausibility the data should be believable eg internal consistency temporal and atemporal comparison
Quality checks of the data conformance are included in the CRF in the form of predefined alerts and errors running during the data input Moreover several additional completeness and plausibility checks eg completeness of variables for each patient plausibility of temporal intervals between different dates etc are implemented in an external web tool connected to the CRF by use of API key capable of executing all data quality checks simultaneously The API key is not transmitted outside the centre it is used only locally to perform data quality checks The results of these checks are available locally for each centre and periodically they will be summarized in reports that the registry coordination team INT will monitor and discuss with each centre
Legal basis of the registry
In Europe the processing of personal data for scientific research can be grounded upon several conditions of lawfulness established in Article 92 of the General Data Protection Regulation GDPR Among these the most relevant ones are
the consent of data subjects Art 92lit a
the pursuing of a substantial public interest on the basis of Union or Member State law Art 92lit g
the pursuing of a scientific research purpose on the basis of Union or Member State law Art 92lit j
The GDPR allows or requires Member States to implement national specifications or derogations from certain rules set out in the GDPR therefore the legal basis of the federated registry will be based in each participating hospital on the laws and regulations of its country
Since the number of patients is inherently low at the hospital level the only way to increase knowledge about EHE and improve the diagnosis treatment and prognosis of this complex and heterogeneous disease is to harmonize and combine real-world data from sarcoma expert centres by leveraging a wide international joined effort In this context a unique opportunity is provided by the European Reference Networks ERNs virtual network established by the EU commission aiming to tackle rare conditions including cancers Among the three ERNs dedicated to cancer EURACAN httpseuracaneu is the one focusing on the 10 families of rare adult solid cancers RACs including soft tissue sarcomas bone sarcomas and gastrointestinal stromal tumour Fostering academic research and promote epidemiological surveillance in rare cancers through setting up of shared registries is recognize as one of ERNs priorities Within the sarcoma domain taking into account the challenges described above priority was given to ultra-rare sarcoma and thanks to the strong connection motivation and support provided by EHE Rare Cancer Charity UK it was decided to start from EHE We believe that in this context the collection of high-quality data by clinical registries will be crucial to improve the understanding of EHE natural history validate and identify new prognostic factors clarify the activity and efficacy of currently available treatment options and eventually provide and external control which might serve as a benchmark for the development of new drugs and support discussion with regulatory authorities
The EURACAN EHE registry is a prospective clinical registry that will collect data from all new patients receiving a pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023 To this aim an EHE-focused clinical record form CRF was developed through the Research Electronic Data Capture REDCap and designed to capture the specific features of this disease
For each patient data collection will include
1 A common baseline including full details on demographic comorbidities special focus on immune-mediated and gynecological diseases concomitant medications physical examination systemic symptoms at presentation tumour-related pain assessment blood tests pathology and molecular features on the diagnostic specimen EHE extension at baseline unifocal disease loco-regional disease systemic metastases
2 Depending on the disease extent detail on staging modalities primary site and size extension of metastatic disease organs involved number of lesions presence and characterization of serosal involvement and effusion treatment surgery radiation therapy medical therapies isolated limb perfusion other locoregional techniques
Although the EHE registry per se does not foresee any collection of pathological samples and or imaging the availability for each enrolled patient of pathological samples massive parallel sequencing data and imaging at the contributing institution will be captured by the CRF in order to facilitate patients identification for future dedicated studies which will imply the use of these data
Given the peculiar biological EHE behavior in absence of any event a mandatory 6-monthly update will be required at all contributing centers In the mandatory 6-monthly update information from the last visit will be recorded regarding physical examination time interval of development of systemic symptoms assessment of tumor-related pain blood tests update on ongoing treatment active surveillance including modalities and timing of radiological monitoring and radiological response
All events will be recorded at the time of the occurrence for unifocal disease local recurrence and metastatic progression for locoregional and metastatic disease systemic progression For every event information will be recorded on physical examination time interval of development of systemic symptoms assessment of tumor-related pain assessment blood tests hemoglobin and fibrinogen radiological modalities detecting progression extent of progression by RECIST 11 and not serosal involvement and or effusion update on ongoing treatment active surveillance
Patient status alive with no evidence of disease alive with disease dead and last follow up will be updated at any data entry
The registry and therefore the electronic CRF have been shaped starting from what have been agreed and reported in the EHE consensus paper from the sarcoma community of experts published in 2021 A registry kick-off meeting was held in Milan the 15th September 2023 involving the EHE prospective clinical registry coordination team all the contributing centers and patients associations EHE Rare Cancer Charity UK EHE Italia and EHE US to present the registry and share common clinical practice guidelines derived from the consensus paper to be followed for the patients with EHE included in the registry
The launch of the EHE prospective clinical registry was shared with all the reference institutions belonging as full members or associated partners to EURACAN sarcoma domain 63 institutions across Europe
The project was also opened to EU institutions not belonging to EURACAN and extra-EU institutions In this case in order to ensure an adequate degree of expertise in the disease the institutions interested in joining the registry were asked to provide the number of new EHE cases molecularly confirmed seen each year over 3 years 2020-2021-2022 and a threshold of at least 20 of EHE national incident cases was selected for participation
As a result of this process 21 institutions joined the registry in September 2023 17 of which belonging to EURACAN from 10 countries
The registry is federated thus data are stored by the health care providers contributing to the registry At the local level data are pseudonymised
Statistical analyses will be performed based on a study protocol Queries will be developed in collaboration with clinical experts to interrogate the EURACAN EHE registry to generate the descriptive statistics and relevant information needed to plan the analyses envisaged by the study protocol
Data quality checks aim to assess whether data values are present if they adhere to specific standard and if they are believable in terms of
Conformance the data should be recorded in agreement with the correct formats eg range of values date formats
Completeness the data should not have missing values or data records
Plausibility the data should be believable eg internal consistency temporal and atemporal comparison
Quality checks of the data conformance are included in the CRF in the form of predefined alerts and errors running during the data input Moreover several additional completeness and plausibility checks eg completeness of variables for each patient plausibility of temporal intervals between different dates etc are implemented in an external web tool connected to the CRF by use of API key capable of executing all data quality checks simultaneously The API key is not transmitted outside the centre it is used only locally to perform data quality checks The results of these checks are available locally for each centre and periodically they will be summarized in reports that the registry coordination team INT will monitor and discuss with each centre
Legal basis of the registry
In Europe the processing of personal data for scientific research can be grounded upon several conditions of lawfulness established in Article 92 of the General Data Protection Regulation GDPR Among these the most relevant ones are
the consent of data subjects Art 92lit a
the pursuing of a substantial public interest on the basis of Union or Member State law Art 92lit g
the pursuing of a scientific research purpose on the basis of Union or Member State law Art 92lit j
The GDPR allows or requires Member States to implement national specifications or derogations from certain rules set out in the GDPR therefore the legal basis of the federated registry will be based in each participating hospital on the laws and regulations of its country
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None