<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01662739</url>
  </required_header>
  <id_info>
    <org_study_id>Donida-1</org_study_id>
    <nct_id>NCT01662739</nct_id>
  </id_info>
  <brief_title>Cremona Population-Based Gastric Tumors Registry</brief_title>
  <official_title>Epidemiological, Clinical and Pathological Characteristics of Gastric Tumors. The Population Based Specialized Registry in Northern Italy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medicina e Arte Onlus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Istituti Ospitalieri di Cremona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Azienda Sanitaria Locale di Cremona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Azienda Ospedaliera Ospedale Maggiore di Crema</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Casa di Cura Figlie di San Camillo di Cremona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Casa di Cura San Camillo di Cremona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Casa di Cura Ancelle della Carità di Cremona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medicina e Arte Onlus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gastric cancer remains one of the leading causes of cancer-related deaths worldwide. There is&#xD;
      difference between different countries in the world in the incidence and outcome. Also Italy&#xD;
      on its inside shows a variability between regions and Lombardy hold the most incidence and&#xD;
      mortality Italian rate, with the province of Cremona as one of the leading area with its&#xD;
      gastric cancer mortality rate. (http://www.aslcremona.it/html/atlante/introduzione.htm).&#xD;
      Tumor specialized registry can be viewed as one of the main strategies for studying and&#xD;
      monitoring the impact of an important cancer diagnosis. In addition the information obtained&#xD;
      from it can be translated into preventive measures and health surveillance that might lead to&#xD;
      a better control of this tumor in a province with a so high mortality rate. Project purpose&#xD;
      is to define the incidence of gastric cancer in the province of Cremona and the correlation&#xD;
      with environmental, familiar, genetic and social factors; to adopt prevention strategies to&#xD;
      reduce the impact of the disease and to create a gastric cancer bio-bank, including blood and&#xD;
      tissue samples, for collaborative research projects regarding molecular and cellular aspects&#xD;
      of gastric cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Gastric cancer (GC) is the 5th most common cancer and the 3rd leading cause of&#xD;
      cancer-related deaths worldwide. GC incidence and mortality rates vary widely across&#xD;
      different geographical areas. In Italy the province of Cremona is characterized by an high&#xD;
      incidence, compared with the national one. For these reason a specialized population based&#xD;
      registry was set up.&#xD;
&#xD;
      Methods: Up to now the collection encompasses all the GC cases diagnosed in Cremona province&#xD;
      from January 1st 2010 until December 31st 2015. The main data sources were represented by the&#xD;
      pathological records and the patient clinical charts. Data were collected following AIRTum&#xD;
      (Associazione Italiana Registri Tumori) and IARC (International Agency for Research on&#xD;
      Cancer) cancer registration recommendations. Territory of Cremona province comprises 3 main&#xD;
      public hospitals and 3 private structures. All of them refer to 2 pathology services. All&#xD;
      these facilities were involved in the project. A minority of patients usually ask for&#xD;
      different surgery and move to neighboring provinces, mainly Milan and Brescia. An official&#xD;
      collaboration with these facilities was signed in order to have the access to the data of&#xD;
      their patients who were inhabitants of the province of Cremona. A multidisciplinary team of&#xD;
      clinicians (oncologists, gastroenterologists, general practitioners, surgeons), pathologists,&#xD;
      geneticists and methodologists (epidemiologists, hygienists) was involved in the project.&#xD;
&#xD;
      The registration of an incident case usually began with the pathological confirmation of&#xD;
      diagnosis of cancer. Subsequently, medical records were obtained. For each case the following&#xD;
      variables were registered: personal and familiar data; imaging studies performed; details on&#xD;
      surgery and other treatments received; host genetic background and biomolecular&#xD;
      characteristic, social and environmental factors. All data were collected, recorded,&#xD;
      protected and processed in accordance to AIRTum-IARC (International Agency for Research on&#xD;
      Cancer) cancer registration recommendations and national privacy laws.&#xD;
&#xD;
      Any age at diagnosis was included. At the time of diagnosis patients had to be inhabitants of&#xD;
      the province of Cremona (districts of Crema, Cremona or Casalmaggiore). Only diagnoses of&#xD;
      primary gastric neoplasms were considered. Precancerous lesions and relapsed tumor diagnoses&#xD;
      were not considered. For the specific purposes of our study, we didn't record cases diagnosed&#xD;
      based on Death Certificate Only (DCO)&quot;in situ&quot; tumors were also included.&#xD;
&#xD;
      Site of the tumor at diagnosis was stomach or gastro-esophageal junction (GEJ), ref. cod.&#xD;
      ICD-X C16, according to the UICC, 7th ed.&#xD;
&#xD;
      All gastric malignancies were considered: gastric cancer; lymphoma; sarcoma and GIST. Gastric&#xD;
      cancer was classified according to the Lauren's classification system, which distinguishes&#xD;
      two main histological types: &quot;intestinal&quot; and &quot;diffuse&quot; . &quot;Mixed&quot; gastric carcinomas composed&#xD;
      of intestinal and diffuse components have also been identified.&#xD;
&#xD;
      The primary tumor location was divided into three groups in consideration not only of the&#xD;
      oncological but also of the surgical approach. Such groups were 1) GEJ-cardia; 2)&#xD;
      body-fundus; 3) antrum-pylorus-angulus.&#xD;
&#xD;
      The TNM classification was recorded and the corresponding pathological stage was determined&#xD;
      according to the 7th edition of the Union for International Cancer Control (UICC) and&#xD;
      hereditary cases according to International GC Linkage Consortium guidelines.&#xD;
&#xD;
      Evaluation of the infection of Helicobacter pylori (HP) was performed by immunohistochemistry&#xD;
      (IHC) in health gastric mucosa using the GIEMSA stain method. The HER-2 oncogene&#xD;
      overexpression was evaluated in tumour gastric mucosa by the IHC method Dako Hercept TestTM.&#xD;
      Results were confirmed by Fluorescent in Situ Hybridization (FISH) when IHC positivity score&#xD;
      was 2.&#xD;
&#xD;
      To individuate Hereditary Diffuse Gastric Cancer (HDGC) cases, criteria by International GC&#xD;
      Linkage Consortium 2010 guidelines were followed.&#xD;
&#xD;
      Incidence, standard errors, and 95% confidence intervals (CI) were calculated according to&#xD;
      the International Agency for Research on Cancer (IARC) general guidelines. As for CIs, the&#xD;
      method that considered the approximation to the Poisson distribution was chosen. Age-specific&#xD;
      incidence rates were stratified into 18 subgroups by 5-year age interval (0 - 4, to 85+&#xD;
      years). Raw age-specific (5-years classes) and age-standardised (age-adjusted) rates were&#xD;
      calculated per 100,000 inhabitants. For raw rates the denominator was the resident population&#xD;
      census at 31st December of each year, available online at the official site of Cremona&#xD;
      province. An age-standardized rate (ASR) is a weighted average of the age-specific (raw)&#xD;
      rate, where the weight is the proportion of individuals in the corresponding age group of a&#xD;
      standard population. Age-standardised rates were calculated using the standard age-structure&#xD;
      of the European (EU) and World (W) standard population. This corrects the potential&#xD;
      confounding effect derived from the differences in age between different populations. The&#xD;
      trend of incidence, expressed as &quot;Annual Percent Change&quot; (APC) was evaluated using Join Point&#xD;
      (National Cancer Institute, Bethesda, MD) in order to identify significant changes. Overall&#xD;
      survival analysis was carried out by Kaplan-Meier methods and statistically significant&#xD;
      differences were evaluated by Log-Rank Test . Survival hazard ratio was evaluated by Cox&#xD;
      regression model, subsequently the testing of the proportion of hazard. Cumulative risks and&#xD;
      other variables, including age at diagnosis, anatomical subsite, morphology of the tumour,&#xD;
      TNM stage at diagnosis, presence of HP infection, HER-2 amplification status, 5-year survival&#xD;
      and 1-year mortality rate were reported too. Descriptive statistics were used to summarize&#xD;
      the data and parametric and non-parametric tests were used to evaluate differences between&#xD;
      groups. Statistical analysis was carried out by STATA 13 software package (Texas, USA). A&#xD;
      p-value less than 0.05 vas considered as statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2010</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Collection of life-style, familiar, clinical, histological and biomolecular data</measure>
    <time_frame>Five Years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Collection of biological samples (blood and cancer tissue samples)</measure>
    <time_frame>Five Years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Analysis of epidemiology, risk factors, family history and unidentified susceptibility genes and proteins</measure>
    <time_frame>Five Years</time_frame>
  </other_outcome>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Gastric Cancer</condition>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Questionnaire</intervention_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and Cancer Tissue Sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Gastric Cancer&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        PATIENTS ELEGIBILY : Any patients age at GC cancer diagnosis was included. Male and female&#xD;
        patients were either included. Healthy volunteers were not included. At the time of&#xD;
        diagnosis of cancer patients must be a province of Cremona inhabitants (districts of Crema,&#xD;
        Cremona or Casalmaggiore). Informed consent signature was required.&#xD;
&#xD;
        TUMOR ELEGIBLY: Diagnosis must be performed from 2010 Juanuary, the 1st to 2013 December,&#xD;
        31st .The diagnosis must be of a infiltrating malignant tumor. The diagnosis should be of a&#xD;
        primary tumor. Precancerous diagnosis were not considered. Recidivate tumor were not&#xD;
        considered. The site of localization of the tumor at diagnosis must be stomach or gastro -&#xD;
        esophageal junction as site of tumor onset.&#xD;
&#xD;
        HDGC ELEGIBILY : Gastric cancer is a known manifestation of inherited cancer predisposition&#xD;
        syndromes similar to hereditary nonpolyposis colon cancer and Li-Fraumeni syndrome.&#xD;
        According to the OMIM database, more than 90 per cent of gastric cancers are sporadic,&#xD;
        whereas less than 10 per cent are hereditary (HDGC). Germline E-cadherin inactivating&#xD;
        mutations in the CDH1 gene are responsible for the development of GC in approximately 30%&#xD;
        of families with the hereditary diffuse gastric cancer syndrome (HDGC). Diagnostic criteria&#xD;
        for HDGC are formulated by the International Gastric Cancer Linkage Consortium in 1999 and&#xD;
        then they are reviewed in 2010. In order to individuate HDGC case and to included them in a&#xD;
        specialist counselling and CDH-1 gene mutation evaluation, criteria by International GC&#xD;
        Linkage Consortium 2010 guidelines were followed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Rodolfo Passalacqua, MD</last_name>
    <email>r.passalacqua@asst-cremona.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>Medical Oncology Department of Istituti Ospitalieri di Cremona</name>
      <address>
        <city>Cremona</city>
        <zip>26100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rodolfo Passalacqua, MD</last_name>
      <email>r.passalacqua@asst-cremona.it</email>
    </contact>
    <investigator>
      <last_name>Rodolfo Passalacqua, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <last_update_submitted>March 3, 2017</last_update_submitted>
  <last_update_submitted_qc>March 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Istituti Ospitalieri di Cremona</investigator_affiliation>
    <investigator_full_name>Bianca Maria Donida, Ph.D</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Population-Based Cancer Registry</keyword>
  <keyword>Stomach</keyword>
  <keyword>Epidemiology</keyword>
  <keyword>Risk Factor</keyword>
  <keyword>Biomolecular Features</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01662739
org study id: Donida-1
nct id: NCT01662739
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Gastric cancer remains one of the leading causes of cancer-related deaths worldwide. There is
      difference between different countries in the world in the incidence and outcome. Also Italy
      on its inside shows a variability between regions and Lombardy hold the most incidence and
      mortality Italian rate, with the province of Cremona as one of the leading area with its
      gastric cancer mortality rate. (http://www.aslcremona.it/html/atlante/introduzione.htm).
      Tumor specialized registry can be viewed as one of the main strategies for studying and
      monitoring the impact of an important cancer diagnosis. In addition the information obtained
      from it can be translated into preventive measures and health surveillance that might lead to
      a better control of this tumor in a province with a so high mortality rate. Project purpose
      is to define the incidence of gastric cancer in the province of Cremona and the correlation
      with environmental, familiar, genetic and social factors; to adopt prevention strategies to
      reduce the impact of the disease and to create a gastric cancer bio-bank, including blood and
      tissue samples, for collaborative research projects regarding molecular and cellular aspects
      of gastric cancer.
Background: Gastric cancer (GC) is the 5th most common cancer and the 3rd leading cause of
      cancer-related deaths worldwide. GC incidence and mortality rates vary widely across
      different geographical areas. In Italy the province of Cremona is characterized by an high
      incidence, compared with the national one. For these reason a specialized population based
      registry was set up.

      Methods: Up to now the collection encompasses all the GC cases diagnosed in Cremona province
      from January 1st 2010 until December 31st 2015. The main data sources were represented by the
      pathological records and the patient clinical charts. Data were collected following AIRTum
      (Associazione Italiana Registri Tumori) and IARC (International Agency for Research on
      Cancer) cancer registration recommendations. Territory of Cremona province comprises 3 main
      public hospitals and 3 private structures. All of them refer to 2 pathology services. All
      these facilities were involved in the project. A minority of patients usually ask for
      different surgery and move to neighboring provinces, mainly Milan and Brescia. An official
      collaboration with these facilities was signed in order to have the access to the data of
      their patients who were inhabitants of the province of Cremona. A multidisciplinary team of
      clinicians (oncologists, gastroenterologists, general practitioners, surgeons), pathologists,
      geneticists and methodologists (epidemiologists, hygienists) was involved in the project.

      The registration of an incident case usually began with the pathological confirmation of
      diagnosis of cancer. Subsequently, medical records were obtained. For each case the following
      variables were registered: personal and familiar data; imaging studies performed; details on
      surgery and other treatments received; host genetic background and biomolecular
      characteristic, social and environmental factors. All data were collected, recorded,
      protected and processed in accordance to AIRTum-IARC (International Agency for Research on
      Cancer) cancer registration recommendations and national privacy laws.

      Any age at diagnosis was included. At the time of diagnosis patients had to be inhabitants of
      the province of Cremona (districts of Crema, Cremona or Casalmaggiore). Only diagnoses of
      primary gastric neoplasms were considered. Precancerous lesions and relapsed tumor diagnoses
      were not considered. For the specific purposes of our study, we didn't record cases diagnosed
      based on Death Certificate Only (DCO)"in situ" tumors were also included.

      Site of the tumor at diagnosis was stomach or gastro-esophageal junction (GEJ), ref. cod.
      ICD-X C16, according to the UICC, 7th ed.

      All gastric malignancies were considered: gastric cancer; lymphoma; sarcoma and GIST. Gastric
      cancer was classified according to the Lauren's classification system, which distinguishes
      two main histological types: "intestinal" and "diffuse" . "Mixed" gastric carcinomas composed
      of intestinal and diffuse components have also been identified.

      The primary tumor location was divided into three groups in consideration not only of the
      oncological but also of the surgical approach. Such groups were 1) GEJ-cardia; 2)
      body-fundus; 3) antrum-pylorus-angulus.

      The TNM classification was recorded and the corresponding pathological stage was determined
      according to the 7th edition of the Union for International Cancer Control (UICC) and
      hereditary cases according to International GC Linkage Consortium guidelines.

      Evaluation of the infection of Helicobacter pylori (HP) was performed by immunohistochemistry
      (IHC) in health gastric mucosa using the GIEMSA stain method. The HER-2 oncogene
      overexpression was evaluated in tumour gastric mucosa by the IHC method Dako Hercept TestTM.
      Results were confirmed by Fluorescent in Situ Hybridization (FISH) when IHC positivity score
      was 2.

      To individuate Hereditary Diffuse Gastric Cancer (HDGC) cases, criteria by International GC
      Linkage Consortium 2010 guidelines were followed.

      Incidence, standard errors, and 95% confidence intervals (CI) were calculated according to
      the International Agency for Research on Cancer (IARC) general guidelines. As for CIs, the
      method that considered the approximation to the Poisson distribution was chosen. Age-specific
      incidence rates were stratified into 18 subgroups by 5-year age interval (0 - 4, to 85+
      years). Raw age-specific (5-years classes) and age-standardised (age-adjusted) rates were
      calculated per 100,000 inhabitants. For raw rates the denominator was the resident population
      census at 31st December of each year, available online at the official site of Cremona
      province. An age-standardized rate (ASR) is a weighted average of the age-specific (raw)
      rate, where the weight is the proportion of individuals in the corresponding age group of a
      standard population. Age-standardised rates were calculated using the standard age-structure
      of the European (EU) and World (W) standard population. This corrects the potential
      confounding effect derived from the differences in age between different populations. The
      trend of incidence, expressed as "Annual Percent Change" (APC) was evaluated using Join Point
      (National Cancer Institute, Bethesda, MD) in order to identify significant changes. Overall
      survival analysis was carried out by Kaplan-Meier methods and statistically significant
      differences were evaluated by Log-Rank Test . Survival hazard ratio was evaluated by Cox
      regression model, subsequently the testing of the proportion of hazard. Cumulative risks and
      other variables, including age at diagnosis, anatomical subsite, morphology of the tumour,
      TNM stage at diagnosis, presence of HP infection, HER-2 amplification status, 5-year survival
      and 1-year mortality rate were reported too. Descriptive statistics were used to summarize
      the data and parametric and non-parametric tests were used to evaluate differences between
      groups. Statistical analysis was carried out by STATA 13 software package (Texas, USA). A
      p-value less than 0.05 vas considered as statistically significant.
observational model: Cohort
time perspective: Prospective
measure: Collection of life-style, familiar, clinical, histological and biomolecular data
time frame: Five Years
measure: Collection of biological samples (blood and cancer tissue samples)
time frame: Five Years
measure: Analysis of epidemiology, risk factors, family history and unidentified susceptibility genes and proteins
time frame: Five Years
intervention type: Behavioral
intervention name: Questionnaire
Blood and Cancer Tissue Sample
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Rodolfo Passalacqua, MD
email: r.passalacqua@asst-cremona.it
facility: 
status: Recruiting
contact: 
investigator: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Istituti Ospitalieri di Cremona
investigator full name: Bianca Maria Donida, Ph.D
investigator title: PhD
mesh term: Stomach Neoplasms