<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/NCT03230240</url>
  </required_header>
  <id_info>
    <org_study_id>MMC2015-62</org_study_id>
    <nct_id>NCT03230240</nct_id>
  </id_info>
  <brief_title>Immunologic Profile of Peritoneal Cancer</brief_title>
  <official_title>Immunologic, Cellular, and Anti-microbial Profiling of Intraperitoneal Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MercyOne Des Moines Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MercyOne Des Moines Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To ascertain immunologic profile of peritoneal cavity and its relationship to immediate&#xD;
      postsurgical outcome (morbidity or the treatment) and long-term outcome (time to recurrence&#xD;
      and survival).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. BACKGROUND:&#xD;
&#xD;
           Tumor-host interaction includes inactivation of immunologic recognition of malignant&#xD;
           cells by a mechanism yet not fully understood. Aneuplodity studies on cells from&#xD;
           different metastatic sites demonstrate increased heterogeneity depending on metastatic&#xD;
           site (Kimball 1997). This suggests that phenotypically different cell populations are&#xD;
           responsible for different metastases and may demonstrate different&#xD;
           sensitivity/resistance to treatment. Kitayama (2015) studied ratio of lymphocytes to&#xD;
           epithelial cell in peritoneal cavity, but used this ratio only as marker of tumor burden&#xD;
           and did not relate it to perioperative outcome.&#xD;
&#xD;
           Investigators have clinically observed a different behavior of peritoneal metastases as&#xD;
           compared to those located in other body sites (Franko 2012, Klaver 2012, Franko 2016).&#xD;
           It is hypothesized that tumor-host interaction and host-treatment response are related&#xD;
           to treatment-related morbidity, early vs. delayed recurrence, and overall survival.&#xD;
&#xD;
           There is a limited literature and research examining the immunologic profile of&#xD;
           intraperitoneal chemotherapy and its relationship to morbidity and future metastatic&#xD;
           sites. Therefore, further knowledge of the biology of different peritoneal surface&#xD;
           metastatic disease is necessary. This, with additional research, may lead to specific&#xD;
           therapies.&#xD;
&#xD;
        2. OBJECTIVES:&#xD;
&#xD;
           To ascertain immunologic profile of peritoneal cavity and its relationship to immediate&#xD;
           postsurgical outcome (morbidity or the treatment) and long-term outcome (time to&#xD;
           recurrence and survival).&#xD;
&#xD;
        3. STUDY POPULATION:&#xD;
&#xD;
           Patients with peritoneal carcinomatosis undergoing intraperitoneal chemotherapy.&#xD;
&#xD;
           3.1 Exclusion criteria: Under age of 18 years, pregnant patients, those unable to&#xD;
           provide consent.&#xD;
&#xD;
        4. SUBJECT RECRUITMENT METHODS:&#xD;
&#xD;
           All patients scheduled to undergo cytoreductive procedure for peritoneal carcinomatosis&#xD;
           in at Mercy Medical Center in Des Moines, IA (MMC). This study will be offered during a&#xD;
           preoperative office or a hospital visit by Dr Franko or Dr Goldman.&#xD;
&#xD;
        5. INFORMED CONSENT:&#xD;
&#xD;
           Attached&#xD;
&#xD;
        6. RESEARCH PROCEDURES:&#xD;
&#xD;
           Liquid samples will be collected and analyzed. We will collect ascites, peritoneal&#xD;
           washout, HIPEC perfusion fluid. Samples will be analyzed using flow cytometry, routine&#xD;
           fluid cytology, and tested for anti-microbial properties.&#xD;
&#xD;
           6.1 Sample labeling:&#xD;
&#xD;
           The following peritoneal fluid sample will be collected:&#xD;
&#xD;
           A - ascites or peritoneal saline washout at the beginning of case B - HIPEC fluid after&#xD;
           pre-heating and immediately before chemotherapy agent provision C, D, E - HIPEC fluid at&#xD;
           30, 60, and 90 minutes of perfusion 6.2 Flow cytometry Fluid samples will be run through&#xD;
           flow cytometry to analyze proportion of CD3, CD4, CD8, CD20, CD34 positive cells.&#xD;
&#xD;
           6.3 Cytology Routine cytology of peritoneal fluid represents standard of care for&#xD;
           malignant disease diagnostics and will be conducted as per usual diagnostic plan.&#xD;
&#xD;
           6.4 Detection of anti-microbial properties Fluid samples will be introduced to bacterial&#xD;
           growth in the microbiology laboratory at MMC. Growth inhibition of standard bacterial&#xD;
           strains (Staphylococcus aureus, Escherichia coli) will be recorded. The samples will&#xD;
           also be sent for flow cytology and possibly chromatography to measure exact&#xD;
           concentrations of chemotherapeutic agent remaining in samples.&#xD;
&#xD;
           6.5 High-performance liquid chromatography A limited number of samples will be analyzed&#xD;
           with high performance liquid chromatography to determine exact chemotherapy&#xD;
           concentration remaining in sample (den Hartigh 1981). This part of the research is&#xD;
           conducted in collaboration with Dr. Brian Gentry at Drake University. Sample provided&#xD;
           for this part of research will be deidentified, date-time-stamped, and Drake's team will&#xD;
           receive no other clinical or demographic information. Re-identification at MMC remains&#xD;
           possible.&#xD;
&#xD;
           To satisfy methodological needs, we will collect each case will provide 2 samples:&#xD;
           Sample B will be a HIPEC perfusate solution at the completion of initial heating up&#xD;
           period collected before adding chemotherapy agent. Sample E will be perfusate at the&#xD;
           completion of HIPEC procedure expected to contain MMC. Sample E is the main research&#xD;
           sample. Sample volume is 5 cc.&#xD;
&#xD;
        7. DATA COLLECTION AND ANALYSIS:&#xD;
&#xD;
           Sample B is obtained before active treatment agent is provided to the solution. It&#xD;
           represents a small withdrawal volume of 5 cc out of approximately 3-5 liter HIPEC&#xD;
           solution used in usual case. Average clinical dosing of carrier solution is 2 liters/m2&#xD;
           of patient's body surface area, therefore representing &lt; 0.2% total HIPEC carrier&#xD;
           solution volume. Sample C &amp; D represent the same volume, but are withdrawn from patient&#xD;
           with active treatment. Given very small volume of each sample no negative effect is&#xD;
           expected, as total sample volume is &lt;0.6% total HIPEC perfusion fluid.&#xD;
&#xD;
           All other research samples are derived only from residual surgical specimen exclusively&#xD;
           obtained for treatment purposes. Data collection will include, but is not limited to,&#xD;
           patient name, gender, age, initial tumor stage, current tumor stage &amp; extent, histology,&#xD;
           prior treatment modalities, and results from flow cytometry, microbiology, and HPLC, and&#xD;
           medical record for 60 months following surgery.&#xD;
&#xD;
        8. POTENTIAL RISKS:&#xD;
&#xD;
           8.1 Risks related to sampling: Some body fluid samples are collected on residual&#xD;
           surgical specimens removed from patient for treatment purpose (samples A and E), and are&#xD;
           independent of research. The exception are Sample B,C,D - the only samples removed from&#xD;
           patient for research purpose only. The volume of each sample is minute, &lt; 0.2% of total&#xD;
           perfusate volume; therefore total sampling volume in ≤0.6% expected perfusate volume.&#xD;
           Given these two facts it is reasonable to assume no expected influence on patients'&#xD;
           outcome.&#xD;
&#xD;
           8.2 Risks related to loss of confidentiality Because identifiable data are collected&#xD;
           there is a potential risk of breach of confidentiality. To protect confidentiality and&#xD;
           minimize risk, research data will be maintained on MMC computers with access restricted&#xD;
           to the core research team and password-protected file. Privacy laws will be maintained.&#xD;
&#xD;
        9. RESEARCH MATERIALS, RECORDS, AND PRIVACY:&#xD;
&#xD;
           Research database will be maintained on MMC computers with privileged access restricted&#xD;
           to the core research team and password-protected file. Privacy laws will be maintained.&#xD;
&#xD;
       10. CONFIDENTIALITY:&#xD;
&#xD;
      No research specimen will be stored. All research specimens will be destroyed in accordance&#xD;
      with usual laboratory procedures.&#xD;
&#xD;
      Electronic data will be maintained until the last analysis is carried out. Access to the data&#xD;
      will be limited to authorized personnel associated with this study.&#xD;
&#xD;
      The samples provided to Drake University are deidentified and cannot be re-identified by&#xD;
      Drake University team. Therefore no confidentiality loss there is expected.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>January 2016</start_date>
  <completion_date type="Anticipated">October 2020</completion_date>
  <primary_completion_date type="Anticipated">October 2020</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>In vitro growth of Staph Aureus and Escherichia coli measured in millimeters of colony forming unit on Agar plate</measure>
    <time_frame>1 year after operation</time_frame>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Carcinomatosis</condition>
  <arm_group>
    <arm_group_label>HIPEC</arm_group_label>
    <description>Patients with carcinomatosis or other peritoneal surface malignancy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HIPEC</intervention_name>
    <description>heated intraIP chemotherapy</description>
    <arm_group_label>HIPEC</arm_group_label>
    <other_name>Hyperthermic intraperitoneal chemotherapy</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      ascites&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with peritoneal carcinomatosis undergoing intraperitoneal chemotherapy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIPEC pt&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  absent consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jan Franko, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MercyOne Des Moines Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MercyOne Des Moines Medical Center</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Franko J, Brahmbhatt R, Tee M, Raman S, Ferrel B, Gorvet M, Andres M. Cellular Immunoprofile of Peritoneal Environment During a HIPEC Procedure. Ann Surg Oncol. 2020 Dec;27(13):5005-5013. doi: 10.1245/s10434-020-08870-3. Epub 2020 Jul 21.</citation>
    <PMID>32696309</PMID>
  </results_reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>February 8, 2016</study_first_submitted>
  <study_first_submitted_qc>July 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 26, 2017</study_first_posted>
  <last_update_submitted>September 20, 2020</last_update_submitted>
  <last_update_submitted_qc>September 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>MercyOne Des Moines Medical Center</investigator_affiliation>
    <investigator_full_name>Jan Franko, MD</investigator_full_name>
    <investigator_title>Surgical Oncologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03230240
org study id: MMC2015-62
nct id: NCT03230240
lead sponsor: 
has dmc: No
To ascertain immunologic profile of peritoneal cavity and its relationship to immediate
      postsurgical outcome (morbidity or the treatment) and long-term outcome (time to recurrence
      and survival).
1. BACKGROUND:

           Tumor-host interaction includes inactivation of immunologic recognition of malignant
           cells by a mechanism yet not fully understood. Aneuplodity studies on cells from
           different metastatic sites demonstrate increased heterogeneity depending on metastatic
           site (Kimball 1997). This suggests that phenotypically different cell populations are
           responsible for different metastases and may demonstrate different
           sensitivity/resistance to treatment. Kitayama (2015) studied ratio of lymphocytes to
           epithelial cell in peritoneal cavity, but used this ratio only as marker of tumor burden
           and did not relate it to perioperative outcome.

           Investigators have clinically observed a different behavior of peritoneal metastases as
           compared to those located in other body sites (Franko 2012, Klaver 2012, Franko 2016).
           It is hypothesized that tumor-host interaction and host-treatment response are related
           to treatment-related morbidity, early vs. delayed recurrence, and overall survival.

           There is a limited literature and research examining the immunologic profile of
           intraperitoneal chemotherapy and its relationship to morbidity and future metastatic
           sites. Therefore, further knowledge of the biology of different peritoneal surface
           metastatic disease is necessary. This, with additional research, may lead to specific
           therapies.

        2. OBJECTIVES:

           To ascertain immunologic profile of peritoneal cavity and its relationship to immediate
           postsurgical outcome (morbidity or the treatment) and long-term outcome (time to
           recurrence and survival).

        3. STUDY POPULATION:

           Patients with peritoneal carcinomatosis undergoing intraperitoneal chemotherapy.

           3.1 Exclusion criteria: Under age of 18 years, pregnant patients, those unable to
           provide consent.

        4. SUBJECT RECRUITMENT METHODS:

           All patients scheduled to undergo cytoreductive procedure for peritoneal carcinomatosis
           in at Mercy Medical Center in Des Moines, IA (MMC). This study will be offered during a
           preoperative office or a hospital visit by Dr Franko or Dr Goldman.

        5. INFORMED CONSENT:

           Attached

        6. RESEARCH PROCEDURES:

           Liquid samples will be collected and analyzed. We will collect ascites, peritoneal
           washout, HIPEC perfusion fluid. Samples will be analyzed using flow cytometry, routine
           fluid cytology, and tested for anti-microbial properties.

           6.1 Sample labeling:

           The following peritoneal fluid sample will be collected:

           A - ascites or peritoneal saline washout at the beginning of case B - HIPEC fluid after
           pre-heating and immediately before chemotherapy agent provision C, D, E - HIPEC fluid at
           30, 60, and 90 minutes of perfusion 6.2 Flow cytometry Fluid samples will be run through
           flow cytometry to analyze proportion of CD3, CD4, CD8, CD20, CD34 positive cells.

           6.3 Cytology Routine cytology of peritoneal fluid represents standard of care for
           malignant disease diagnostics and will be conducted as per usual diagnostic plan.

           6.4 Detection of anti-microbial properties Fluid samples will be introduced to bacterial
           growth in the microbiology laboratory at MMC. Growth inhibition of standard bacterial
           strains (Staphylococcus aureus, Escherichia coli) will be recorded. The samples will
           also be sent for flow cytology and possibly chromatography to measure exact
           concentrations of chemotherapeutic agent remaining in samples.

           6.5 High-performance liquid chromatography A limited number of samples will be analyzed
           with high performance liquid chromatography to determine exact chemotherapy
           concentration remaining in sample (den Hartigh 1981). This part of the research is
           conducted in collaboration with Dr. Brian Gentry at Drake University. Sample provided
           for this part of research will be deidentified, date-time-stamped, and Drake's team will
           receive no other clinical or demographic information. Re-identification at MMC remains
           possible.

           To satisfy methodological needs, we will collect each case will provide 2 samples:
           Sample B will be a HIPEC perfusate solution at the completion of initial heating up
           period collected before adding chemotherapy agent. Sample E will be perfusate at the
           completion of HIPEC procedure expected to contain MMC. Sample E is the main research
           sample. Sample volume is 5 cc.

        7. DATA COLLECTION AND ANALYSIS:

           Sample B is obtained before active treatment agent is provided to the solution. It
           represents a small withdrawal volume of 5 cc out of approximately 3-5 liter HIPEC
           solution used in usual case. Average clinical dosing of carrier solution is 2 liters/m2
           of patient's body surface area, therefore representing < 0.2% total HIPEC carrier
           solution volume. Sample C & D represent the same volume, but are withdrawn from patient
           with active treatment. Given very small volume of each sample no negative effect is
           expected, as total sample volume is <0.6% total HIPEC perfusion fluid.

           All other research samples are derived only from residual surgical specimen exclusively
           obtained for treatment purposes. Data collection will include, but is not limited to,
           patient name, gender, age, initial tumor stage, current tumor stage & extent, histology,
           prior treatment modalities, and results from flow cytometry, microbiology, and HPLC, and
           medical record for 60 months following surgery.

        8. POTENTIAL RISKS:

           8.1 Risks related to sampling: Some body fluid samples are collected on residual
           surgical specimens removed from patient for treatment purpose (samples A and E), and are
           independent of research. The exception are Sample B,C,D - the only samples removed from
           patient for research purpose only. The volume of each sample is minute, < 0.2% of total
           perfusate volume; therefore total sampling volume in ≤0.6% expected perfusate volume.
           Given these two facts it is reasonable to assume no expected influence on patients'
           outcome.

           8.2 Risks related to loss of confidentiality Because identifiable data are collected
           there is a potential risk of breach of confidentiality. To protect confidentiality and
           minimize risk, research data will be maintained on MMC computers with access restricted
           to the core research team and password-protected file. Privacy laws will be maintained.

        9. RESEARCH MATERIALS, RECORDS, AND PRIVACY:

           Research database will be maintained on MMC computers with privileged access restricted
           to the core research team and password-protected file. Privacy laws will be maintained.

       10. CONFIDENTIALITY:

      No research specimen will be stored. All research specimens will be destroyed in accordance
      with usual laboratory procedures.

      Electronic data will be maintained until the last analysis is carried out. Access to the data
      will be limited to authorized personnel associated with this study.

      The samples provided to Drake University are deidentified and cannot be re-identified by
      Drake University team. Therefore no confidentiality loss there is expected.
observational model: Cohort
time perspective: Prospective
measure: In vitro growth of Staph Aureus and Escherichia coli measured in millimeters of colony forming unit on Agar plate
time frame: 1 year after operation
arm group label: HIPEC
description: Patients with carcinomatosis or other peritoneal surface malignancy
intervention type: Drug
intervention name: HIPEC
description: heated intraIP chemotherapy
arm group label: HIPEC
other name: Hyperthermic intraperitoneal chemotherapy
ascites
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Jan Franko, MD, PhD
role: Principal Investigator
affiliation: MercyOne Des Moines Medical Center
facility: 
country: United States
citation: Franko J, Brahmbhatt R, Tee M, Raman S, Ferrel B, Gorvet M, Andres M. Cellular Immunoprofile of Peritoneal Environment During a HIPEC Procedure. Ann Surg Oncol. 2020 Dec;27(13):5005-5013. doi: 10.1245/s10434-020-08870-3. Epub 2020 Jul 21.
PMID: 32696309
responsible party type: Principal Investigator
investigator affiliation: MercyOne Des Moines Medical Center
investigator full name: Jan Franko, MD
investigator title: Surgical Oncologist
mesh term: Carcinoma
sharing ipd: No