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JOURNAL ONKOLOGIE – STUDIE
EURACAN

The Head and Neck Registry of the European Reference Network on Rare Adult Solid Cancers

Rekrutierend

NCT-Nummer:
NCT05483374

Studienbeginn:
Mai 2022

Letztes Update:
04.04.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Head and Neck Neoplasms, Salivary Gland Neoplasms, Paranasal Sinus Neoplasms, Nasopharyngeal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Collaborator:
Associazione Italiana Oncologia Cervico Cefalica, Ministry of Health, Italy, European Union, Alleanza Contro il Cancro,

Studienleiter

Annalisa Trama, MD
Principal Investigator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Kontakt

Lucia Buratti
Kontakt:
Phone: 0223902901
Phone (ext.): +39
E-Mail: EURACANregistry@istitutotumori.mi.it» Kontaktdaten anzeigen

Studienlocations
(3 von 12)

Assistance Publique-Hôpitaux de Paris - Hôpital Tenon
75020 Paris
FranceNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Bertrand Baujat
Phone: 15601641
Phone (ext.): +33
E-Mail: Bertrand.baujat@aphp.fr» Ansprechpartner anzeigen
Fondazione IRCCS Istituto Nazionale dei Tumori
20133 Milan
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Simone Bonfarnuzzo
Phone: 02 2390 3562
Phone (ext.): +39
E-Mail: simone.bonfarnuzzo@istitutotumori.mi.it» Ansprechpartner anzeigen
Centro Nazionale di Adroterapia Oncologica
27100 Pavia
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Nadia Facchinetti
Phone: 0382-078 406
Phone (ext.): +39
E-Mail: nadia.facchinetti@cnao.it» Ansprechpartner anzeigen
IRCCS Istituto Nazionale Tumori Regina Elena
00144 Roma
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Valentina Manciocco
Phone: 06 52664488
Phone (ext.): +39
E-Mail: valentina.manciocco@ifo.it» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

Despite the rarity of each of the 198 identified rare cancers, collectively they represent

24% of all new cancer cases diagnosed in the EU28/yearly. Differences in survival for rare

cancers exist across European countries suggesting the existence of inequalities in

healthcare. Rare cancers in general get less scientific consideration and financial support

than their more common counterparts. The generation of clinical evidence is more difficult

due to the difficulties of conducting clinical trials for to the small number of patients and

the paucity of accessible data, including data from cancer registries.

There is a wide consensus that to support clinical research on rare cancers, clinical

registries should be developed within networks specializing in rare cancers. In the EU, a

unique opportunity is provided by the European Reference Networks (ERNs). The ERNs are

virtual networks of selected institutions targeting rare conditions. Three ERNs are dedicated

to rare cancers: EuroBloodNet for rare haematological diseases, PaedCan for paediatric

cancers and EURACAN for rare adult solid cancers ( https://euracan.eu/).

An EU-supported project Starting an Adult Rare Tumour Registry (STARTER) began on April 1st

2020 to develop the EURACAN registry. The registry initiated on the rare head and neck

cancers including nasal cavity and paranasal sinuses (incidence rate 0.5/100,000),

nasopharynx (incidence rate 0.5/100,000), salivary gland (incidence rate 1.5/100,000) and

middle ear cancers (incidence rate 0.03/100,000), corresponding to 2,500, 2,500, about 8,000

and about 200 new cases/year in Europe, respectively

(http://rarecarenet.istitutotumori.mi.it/analysis.php). Cancer care for head and neck cancers

is complex in particular for the rare ones. Knowledge is limited, diseases are complex and

often need multidisciplinary approach. Moreover, while most head and neck cancers are

predominantly squamous cell carcinomas, salivary gland tumours include more than 20 distinct

histological subtypes. Thus, heterogeneity add complexity to the rarity.

Against this background, the EURACAN registry on rare head and neck cancers was set up with

the following objectives:

1. to help describe the natural history of rare head and neck cancers;

2. to evaluate factors that influence prognosis;

3. to assess treatment effectiveness;

4. to measure indicators of quality of care.

Furthermore, the registry aims to collect information, where available, on the storage of

biological samples at the premises of the participating healthcare providers (HCPs). This

will facilitate future studies on rare head and neck cancers biology.

The registry is designed to prospectively collect clinical data derived from diagnostic tests

and treatments performed by the HCP as part of patient management. The data collected for the

registry will not entail further examinations or admissions to the HCP and/or additional

appointments to those normally provided. In other words, it will be an observational,

real-world registry.

The registry will exploit data available from:

- national or regional registries/databases (DBs) dedicated to rare head and neck cancers

(i.e. nasopharynx; nasal cavity and paranasal sinuses; salivary gland; and middle ear

cancers)

- HCP registries/DBs;

- ad hoc data collection by HCPs.

The registry is federated thus, data are stored by the data provider. At the local level,

data are pseudonymised.

The Personal Health Train (PHT) enables data from multiple organizations to be analysed

without identifiable data leaving the organization. By keeping data at its source, no copies

of datasets are generated and/or shared with third parties. Vantage6 is the open source

implementation of the PHT (https://www.vantage6.ai). Vantage6 uses the mathematical principle

of "federated learning" which is based on the mathematical principle of splitting

computations into (a) parts at the station (local HCP or registry) and (b) a central part.

The stations share sub-computations with the central server only. If federated learning does

not work, the data, after quality validation, will be anonymised and sent to the coordination

centre (i.e. National Cancer Institute of Milan [Fondazione IRCCS Istituto Nazionale dei

Tumori, Milan-INT]).

Data analyses plan The data analyses will include descriptive statistics showing frequency

and patterns of patients' and cancers' variables; analytical analyses investigating the

association of patients/disease and/or treatment characteristics and health outcomes.

Descriptive statistics will be used to reconstruct the natural history of rare head and neck

cancers (e.g. primary tumour growth rate and pattern, its metastatic dissemination, growth of

metastases, association with other diseases etc.) and to report about quality of care.

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 second primary cancer. Variables to include in the multivariable regression

model will be selected based on the results of univariable analysis. The role of confounding

of other covariates will be evaluated using stratified analysis or sensitivity analysis.

To assess treatment effectiveness, multivariable models, propensity score adjustment and

progression-free survival will be performed.

High proportion of missing data threaten the validity of the inferences/prognostic models.

Thus, a maximum of 10% of missing data will be allowed and missing data will be imputed using

strategy such as unconditional/conditional mean or expectation maximum.

Sample size This is an observational clinical registry which implies a long-term data

collection lasting until all the registry objectives are met. Being this registry an

observational one, there won't be any tipe of sampling, therefore all the patients that meet

the eligibility criteria will be selected. Only HCPs that treat at least 100 cases a year of

all rare head and neck cancers are EURACAN member. As of April 2022, the registry is

activating 10 HCPs and, with time, is envisioning to at least duplicate the number of data

providers. Considering that we expected 6 centres in Italy, 2 centres in Germany, 1 centre in

Czech Republic, 1 centre in Spain, 2 centres in France (400 cases per year)and the whole rare

head and neck cases in The Netherlands (300 patients yearly, based on incidence estimations),

we expect about 1700 patients with a rare head and neck cancer yearly.

Due to the observational nature of the registry, sample size justification is based on the

precision of the estimates presented in terms of width of two-sided 95% Confidence Interval

(CI) for a single proportion using the Simple Asymptotic method (in case of categorical

variables) and in form of normal distribution for means (in case of continuous variables).

Thus, for example, for a categorical endpoint (eg, proportion) a sample size of 80 patients

(e.g. middle ear cases in 4 years) will achieve a maximum width of 95% CI on estimated

proportions of 23.4% (i.e. estimated proportion +/- 11.7%). For continuous endpoints, a

sample size of 80 patients will achieve a maximum width of 95% CI on estimated means of

0.46*SD (i.e. estimated mean +/- 0.23*SD, where SD=Standard Deviation).

For the analytical questions involving several different outputs and variables, it is not

possible to define a summary of the sample size calculation. For this reason ad hoc analysis

plans for each research question are envisioned.

Data quality checks Data quality checks aim to assess whether data value are present, valid

and believable in terms of validity, plausibility and completeness. Validity and plausibility

checks are embedded in the electronic case report form (CRF) in the form of alerts and errors

during the data input. Additional checks are implemented in R. The R script, including the

checks is downloaded locally from an online instruction repository. The R script extracts

from the Research Electronic Data Capture (RedCap) (the IT solution used for the registry

CRF) all the completed cases, stores a copy of the DB in the dedicated local server and runs

the checks locally. The results of these checks are summarized in two reports: a summary and

an individual report. Thanks to the Vantage6 software, the two reports (not the data) will

reach the registry coordination team (INT) to be monitored and discussed with each data

provider.

After the corrections made by the data providers, all checks will be re-run and quality

reports reviewed by INT. Interaction with data providers will be reiterated until sufficient

data quality is achieved. The DB with sufficient data quality will be saved and used for the

federated learning analysis. These checks will be performed annually and will ensure high

data quality within a federated DB.

Data to be collected Following the EURACAN registry objectives, data will be prospectively

collected on patient characteristics, exposure and outcomes. Patient characteristics are

descriptive patient data, such as patient demographics, including lifestyle, medical history,

health status, etc. The registry will not collect genetic data. Exposure data focus on the

disease, devices, procedures, treatments or services of interest. Outcome data describe

patient outcomes (e.g. survival, progression, progression-free survival, death, etc.). In

addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be

also collected

(https://euracan.eu/research/starter/rare-head-and-neck-cancer-registry/#codebook).

Pitfalls There is a risk of limited representativeness due to the hospital-based nature of

the registry and to the fact that hospital contributing to the registry are expert centres

for these rare cancers. Representativeness of the registry will be tested comparing the

registry data with population-based data in terms of relevant variables (eg. age, stage,

prognosis). Adequate statistical (eg. marginal structural model) methods will be used if

time-varying treatments/confounders and confounding by indication (selective prescribing)

will be present, not to raise methodological problems.

Directed acyclic graphs can also be useful to identify the source of bias and will be

utilized in the definitions of the path between covariates.

Clinical Follow-up could be an issue but active search of the life status of the patients

will be guaranteed.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses;

salivary gland cancer in large and small salivary glands; and middle ear (i.e.

squamous carcinoma; adenocarcinoma; neuroendocrine; adenosquamous carcinoma,

teratocarcinosarcoma, NUT carcinoma, odontogenic tumors) + neuroendocrine and

adenocarcinoma in hypopharynx; oropharynx; larynx; oral cavity and lip + odontogenic

carcinoma in oral cavity.

- Adult patients (aged ≥18 years).

- Diagnosis performed or verified by the expert centre entering the patient information

in the registry.

- Patients entering the HCP at any clinical phase of the disease (diagnosis, treatment

of primary cancer, treatment of recurrence, treatment of M+ etc.). The HCP can decide,

based on its resources, the number of patients on whom it can collect data.

- New patients managed by the HCP from 2021 onwards plus patients managed by the HCP,

who are actively followed up at the hospital, with year of diagnosis dating back to

maximum 2018.

Exclusion Criteria:

• Patients (aged < 18 years)

Studien-Rationale

Primary outcome:

1. Overall survival (Time Frame - 1 year):
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

2. Disease free survival (Time Frame - 1 year):
The length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer.

3. The percentage of patients whose cancer shrinks or disappears after treatment. Treatment response expressed as a complete response; partial response; stable disease; progression based on clinical judgment on imaging. (Time Frame - 1 year):
A change related to treatment

4. Incidence of cancer treatment adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) (Time Frame - 1 year):
Any unexpected medical problem that happens during treatment with a drug or other therapy.

5. Percentage of patients with surgical complications as assessed by the Clavien-Dindo Classification (Time Frame - 1 year):
Any deviation from the ideal postoperative course that is not inherent in the procedure and does not comprise a failure to cure.

6. Percentage of patients treated according to clinical practice guidelines for head and neck cancer (Time Frame - 1 year):
Adherence to clinical practice guidelines

Studien-Arme

  • epithelial tumours of nasal cavity and paranasal sinus
    adult patients diagnosed with nasal cavity and paranasal sinus cancers (any stage of disease)
  • epithelial tumours of nasopharynx
    adult patients diagnosed with nasopharyngeal cancers (any stage of disease)
  • minor and major salivary gland tumours
    adult patients diagnosed with minor or major salivary gland cancers (any stage of disease)
  • middel ear tumours
    adult patients diagnosed with cancers of the middle ear (any stage of disease)

Geprüfte Regime

  • observation:
    Not applicable, it is an observational registry

Quelle: ClinicalTrials.gov


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