<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/NCT03246321</url>
  </required_header>
  <id_info>
    <org_study_id>NL60405.100.17</org_study_id>
    <secondary_id>2017-000927-29</secondary_id>
    <secondary_id>NTR6603</secondary_id>
    <secondary_id>ISRCTN89947480</secondary_id>
    <secondary_id>NL60405.100.17</secondary_id>
    <nct_id>NCT03246321</nct_id>
  </id_info>
  <brief_title>PIPAC for Peritoneal Metastases of Colorectal Cancer</brief_title>
  <acronym>CRC-PIPAC</acronym>
  <official_title>Repetitive Electrostatic Pressurised Intraperitoneal Aerosol Chemotherapy With Oxaliplatin (ePIPAC-OX) as a Palliative Monotherapy for Isolated Unresectable Colorectal Peritoneal Metastases: Protocol of a Multicentre, Open-label, Single-arm, Phase II Study (CRC-PIPAC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Koen Rovers</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Catharina Ziekenhuis Eindhoven</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is multicentre, open-label, single-arm phase II study that investigates the feasibility,&#xD;
      safety, tolerability, preliminary efficacy, costs, and pharmacokinetics or repetitive&#xD;
      electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC-OX) as a palliative&#xD;
      monotherapy for patients with isolated unresectable colorectal peritoneal metastases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with&#xD;
      oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with&#xD;
      isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide.&#xD;
      However, little is known about its feasibility, safety, tolerability, efficacy, costs, and&#xD;
      pharmacokinetics in this setting.&#xD;
&#xD;
      Objectives: to prospectively explore the feasibility, safety, tolerability, preliminary&#xD;
      efficacy, costs, and pharmacokinetic profile of repetitive ePIPAC-OX as a palliative&#xD;
      monotherapy for isolated unresectable colorectal PM under controlled circumstances.&#xD;
&#xD;
      Study design: multicentre, open-label, single-arm, phase II study.&#xD;
&#xD;
      Setting: two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM.&#xD;
&#xD;
      Study population: adults who have a World Health Organisation (WHO) performance status of 0&#xD;
      or 1, adequate organ functions, histologically or cytologically confirmed unresectable PM of&#xD;
      a colorectal or appendiceal carcinoma, no systemic metastases, no symptoms of&#xD;
      gastrointestinal obstruction, no contraindications for the planned intervention, and no&#xD;
      previous pressurised intraperitoneal aerosol chemotherapy (PIPAC).&#xD;
&#xD;
      Intervention: instead of standard palliative treatment, enrolled patients receive&#xD;
      laparoscopy-controlled ePIPAC-OX (92 mg/m2 body-surface area [BSA]) with intravenous&#xD;
      leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four&#xD;
      weeks after each procedure, patients undergo clinical, radiological, and biochemical&#xD;
      evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease&#xD;
      progression, after which standard palliative treatment is (re)introduced.&#xD;
&#xD;
      Outcomes: the primary outcome is the number of patients with major toxicity (grade ≥3&#xD;
      according to the Common Terminology Criteria for Adverse Events v4.0) up to four weeks after&#xD;
      the last procedure. Secondary outcomes are the environmental safety of ePIPAC-OX,&#xD;
      procedure-related characteristics, the number of procedures in each patient and reasons for&#xD;
      discontinuation, minor toxicity, organ-specific toxicity, postoperative complications,&#xD;
      hospital stay, readmissions, quality of life, costs, progression-free survival, overall&#xD;
      survival, and the radiological, histopathological, cytological, biochemical, and macroscopic&#xD;
      tumour response. Atomic absorption spectrophotometry is used to measure concentrations of&#xD;
      oxaliplatin in plasma, plasma ultrafiltrate, urine, ascites, PM, and normal peritoneum during&#xD;
      and after ePIPAC-OX.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">October 1, 2019</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Major toxicity</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade III-V, up to 4 weeks after the last ePIPAC-OX</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Minor toxicity</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade II, up to 4 weeks after the last ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ-specific toxicity</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of patients that develops bone marrow, kidney, or liver function disorders, up to four weeks after the last ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major postoperative complications</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of patients with Clavien-Dindo grade III-V postoperative complications, up to four weeks after the last ePIPAC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor postoperative complications</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of patients with Clavien-Dindo grade II postoperative complications, up to four weeks after the last ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital stay</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of days between ePIPAC-OX and initial discharge, up to four weeks after the last ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Readmissions</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of hospital admissions after initial discharge after ePIPAC-OX, up to four weeks after the last ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiological tumour response</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Number of patients with radiological response/stable disease/progression, based on central review of thoracoabdominal CT and diffusion-weighted MRI at baseline and four weeks after each ePIPAC-OX, performed by two independent radiologists blinded to clinical outcomes (classification not defined a priori)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histopathological tumour response</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 12 weeks</time_frame>
    <description>Peritoneal Regression Grading Score (PRGS), based on central review of collected peritoneal biopsies during each ePIPAC-OX, performed by two independent pathologists blinded to clinical outcomes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytological tumour response</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 12 weeks</time_frame>
    <description>Number of patients with positive/negative cytology, based on collected ascites or peritoneal washing cytology during each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macroscopic tumour response</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 12 weeks</time_frame>
    <description>Peritoneal Cancer Index and ascites volume during each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical tumour response</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Tumour marker value measured at baseline, each postoperative day, and four weeks after each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: EQ-5D-5L</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>EQ-5D-5L at baseline and one and four weeks after each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: QLQ-C30</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>QLQ-C30 at baseline and one and four weeks after each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life: QLQ-CR29</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>QLQ-CR29 at baseline and one and four weeks after each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Costs</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 16 weeks</time_frame>
    <description>Costs of treatment, based on questionnaires (iMTA PCQ, iMTA MCQ) four weeks after each ePIPAC-OX, derived from the Dutch costing guidelines for health care research at the time of analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Time between enrolment and clinical, radiological, or macroscopic progression, or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>24 months</time_frame>
    <description>Time between enrolment and death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Environmental safety of ePIPAC-OX</measure>
    <time_frame>1 week (measured only during the first three procedures in the study)</time_frame>
    <description>Platinum concentrations in the air of the operating room and on the surface of the operating room during ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 13 weeks</time_frame>
    <description>Platinum concentrations in plasma and plasma ultrafiltrate (collected before ePIPAC-OX and 5, 10, 20, 30, 60, 120, 240, 360, and 1080 minutes after oxaliplatin injection), urine (collected before ePIPAC-OX and on postoperative days 1, 3, 5, and 7), and two pieces of normal peritoneum and two peritoneal metastases collected during each ePIPAC-OX.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure-related characteristics: intraoperative complications</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 12 weeks</time_frame>
    <description>Number of procedures with intraoperative complications determined during each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure-related characteristics: adhesions</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 12 weeks</time_frame>
    <description>Zühlke score determined during each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure-related characteristics: operating time</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 12 weeks</time_frame>
    <description>Operating time in minutes determined during each ePIPAC-OX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure-related characteristics: blood loss</measure>
    <time_frame>Expected (in case of three ePIPAC-OX): 12 weeks</time_frame>
    <description>Blood loss in minutes determined during each ePIPAC-OX</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Colorectal Neoplasms</condition>
  <condition>Peritoneal Neoplasms</condition>
  <condition>Appendiceal Neoplasms</condition>
  <condition>Peritoneal Carcinomatosis</condition>
  <arm_group>
    <arm_group_label>repetitive ePIPAC-OX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>repetitive ePIPAC-OX</intervention_name>
    <description>Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) (92 mg/m2 body-surface area [BSA]) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four weeks after each procedure, patients undergo clinical, radiological, and biochemical evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease progression, after which standard palliative treatment is (re)considered.</description>
    <arm_group_label>repetitive ePIPAC-OX</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Eligible patients are adults who have:&#xD;
&#xD;
          -  a World Health Organisation (WHO) performance status of ≤1;&#xD;
&#xD;
          -  histological or cytological proof of PM of a colorectal or appendiceal carcinoma;&#xD;
&#xD;
          -  unresectable disease determined by abdominal computed tomography (CT) and a diagnostic&#xD;
             laparoscopy or laparotomy;&#xD;
&#xD;
          -  adequate organ functions (haemoglobin ≥5.0 mmol/L, neutrophils ≥1.5 x 109/L, platelets&#xD;
             ≥100 x 109/L, serum creatinine &lt;1.5 x ULN, creatinine clearance ≥30 ml/min, and liver&#xD;
             transaminases &lt;5 x ULN);&#xD;
&#xD;
          -  no symptoms of gastrointestinal obstruction;&#xD;
&#xD;
          -  no radiological evidence of systemic metastases;&#xD;
&#xD;
          -  no contraindications for oxaliplatin or 5-fluorouracil/leucovorin;&#xD;
&#xD;
          -  no contraindications for a laparoscopy;&#xD;
&#xD;
          -  no previous PIPAC-procedures.&#xD;
&#xD;
        Enrolled patients are excluded from the analyses in case they did not receive a first&#xD;
        ePIPAC-OX, e.g.:&#xD;
&#xD;
          -  due to systemic metastases on baseline thoracoabdominal CT, or;&#xD;
&#xD;
          -  due to non-access during first ePIPAC-OX, or;&#xD;
&#xD;
          -  due to resectable disease during first ePIPAC-OX.&#xD;
&#xD;
        Importantly, enrolment is allowed for patients with an unresected primary tumour (if&#xD;
        asymptomatic) and for patients in various lines of palliative treatment, including patients&#xD;
        who refuse, have not had, or do not qualify for first-line palliative systemic therapy. All&#xD;
        potentially eligible patients are discussed by a multidisciplinary team. Enrolled patients&#xD;
        are informed about the potential consequences of postponing or discontinuing standard&#xD;
        palliative treatment by a medical oncologist prior to enrolment.&#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_official>
    <last_name>Ignace de Hingh, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Catharina Hospital, Eindhoven, Netherlands</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Djamila Boerma, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St Antonius Hospital, Nieuwegein, Netherlands</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Catharina Hospital</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Antonius Hospital</name>
      <address>
        <city>Nieuwegein</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Giger-Pabst U, Tempfer CB. How to Perform Safe and Technically Optimized Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Experience After a Consecutive Series of 1200 Procedures. J Gastrointest Surg. 2018 Dec;22(12):2187-2193. doi: 10.1007/s11605-018-3916-5. Epub 2018 Aug 21.</citation>
    <PMID>30132291</PMID>
  </reference>
  <reference>
    <citation>Tempfer C, Giger-Pabst U, Hilal Z, Dogan A, Rezniczek GA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer. Arch Gynecol Obstet. 2018 Aug;298(2):243-257. doi: 10.1007/s00404-018-4784-7. Epub 2018 Jun 4.</citation>
    <PMID>29869089</PMID>
  </reference>
  <reference>
    <citation>Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hubner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg. 2017 May;104(6):669-678. doi: 10.1002/bjs.10521.</citation>
    <PMID>28407227</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>October 14, 2019</last_update_submitted>
  <last_update_submitted_qc>October 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Catharina Ziekenhuis Eindhoven</investigator_affiliation>
    <investigator_full_name>Koen Rovers</investigator_full_name>
    <investigator_title>MD, Coordinating Investigator</investigator_title>
  </responsible_party>
  <keyword>Colorectal Neoplasms</keyword>
  <keyword>Peritoneal Neoplasms</keyword>
  <keyword>Intraperitoneal Injections</keyword>
  <keyword>Laparoscopy</keyword>
  <keyword>Aerosols</keyword>
  <keyword>Chemotherapy, Cancer, Regional Perfusion</keyword>
  <keyword>Antineoplastic Agents</keyword>
  <keyword>Leucovorin</keyword>
  <keyword>Fluorouracil</keyword>
  <keyword>Platinum</keyword>
  <keyword>Intraoperative Complications</keyword>
  <keyword>Postoperative Complications</keyword>
  <keyword>Drug-Related Side Effects and Adverse Reactions</keyword>
  <keyword>Disease-free survival</keyword>
  <keyword>Survival</keyword>
  <keyword>Mortality</keyword>
  <keyword>Quality of Life</keyword>
  <keyword>Costs and Cost Analysis</keyword>
  <keyword>Translational Medical Research</keyword>
  <keyword>Clinical Trials, Phase II as topic</keyword>
  <keyword>PIPAC</keyword>
  <keyword>Pressurized Intraperitoneal Aerosol Chemotherapy</keyword>
  <keyword>Pressurised Intraperitoneal Aerosol Chemotherapy</keyword>
  <keyword>Peritoneum</keyword>
  <keyword>Cecal Neoplasms</keyword>
  <keyword>Oxaliplatin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Peritoneal Neoplasms</mesh_term>
    <mesh_term>Appendiceal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Available on request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>End of the study</ipd_time_frame>
    <ipd_access_criteria>Available on request</ipd_access_criteria>
  </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/NCT03246321
org study id: NL60405.100.17
secondary id: 2017-000927-29
secondary id: NTR6603
secondary id: ISRCTN89947480
secondary id: NL60405.100.17
nct id: NCT03246321
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is multicentre, open-label, single-arm phase II study that investigates the feasibility,
      safety, tolerability, preliminary efficacy, costs, and pharmacokinetics or repetitive
      electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC-OX) as a palliative
      monotherapy for patients with isolated unresectable colorectal peritoneal metastases.
Rationale: repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with
      oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with
      isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide.
      However, little is known about its feasibility, safety, tolerability, efficacy, costs, and
      pharmacokinetics in this setting.

      Objectives: to prospectively explore the feasibility, safety, tolerability, preliminary
      efficacy, costs, and pharmacokinetic profile of repetitive ePIPAC-OX as a palliative
      monotherapy for isolated unresectable colorectal PM under controlled circumstances.

      Study design: multicentre, open-label, single-arm, phase II study.

      Setting: two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM.

      Study population: adults who have a World Health Organisation (WHO) performance status of 0
      or 1, adequate organ functions, histologically or cytologically confirmed unresectable PM of
      a colorectal or appendiceal carcinoma, no systemic metastases, no symptoms of
      gastrointestinal obstruction, no contraindications for the planned intervention, and no
      previous pressurised intraperitoneal aerosol chemotherapy (PIPAC).

      Intervention: instead of standard palliative treatment, enrolled patients receive
      laparoscopy-controlled ePIPAC-OX (92 mg/m2 body-surface area [BSA]) with intravenous
      leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four
      weeks after each procedure, patients undergo clinical, radiological, and biochemical
      evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease
      progression, after which standard palliative treatment is (re)introduced.

      Outcomes: the primary outcome is the number of patients with major toxicity (grade ≥3
      according to the Common Terminology Criteria for Adverse Events v4.0) up to four weeks after
      the last procedure. Secondary outcomes are the environmental safety of ePIPAC-OX,
      procedure-related characteristics, the number of procedures in each patient and reasons for
      discontinuation, minor toxicity, organ-specific toxicity, postoperative complications,
      hospital stay, readmissions, quality of life, costs, progression-free survival, overall
      survival, and the radiological, histopathological, cytological, biochemical, and macroscopic
      tumour response. Atomic absorption spectrophotometry is used to measure concentrations of
      oxaliplatin in plasma, plasma ultrafiltrate, urine, ascites, PM, and normal peritoneum during
      and after ePIPAC-OX.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Major toxicity
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade III-V, up to 4 weeks after the last ePIPAC-OX
measure: Minor toxicity
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade II, up to 4 weeks after the last ePIPAC-OX
measure: Organ-specific toxicity
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of patients that develops bone marrow, kidney, or liver function disorders, up to four weeks after the last ePIPAC-OX
measure: Major postoperative complications
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of patients with Clavien-Dindo grade III-V postoperative complications, up to four weeks after the last ePIPAC
measure: Minor postoperative complications
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of patients with Clavien-Dindo grade II postoperative complications, up to four weeks after the last ePIPAC-OX
measure: Hospital stay
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of days between ePIPAC-OX and initial discharge, up to four weeks after the last ePIPAC-OX
measure: Readmissions
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of hospital admissions after initial discharge after ePIPAC-OX, up to four weeks after the last ePIPAC-OX
measure: Radiological tumour response
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Number of patients with radiological response/stable disease/progression, based on central review of thoracoabdominal CT and diffusion-weighted MRI at baseline and four weeks after each ePIPAC-OX, performed by two independent radiologists blinded to clinical outcomes (classification not defined a priori)
measure: Histopathological tumour response
time frame: Expected (in case of three ePIPAC-OX): 12 weeks
description: Peritoneal Regression Grading Score (PRGS), based on central review of collected peritoneal biopsies during each ePIPAC-OX, performed by two independent pathologists blinded to clinical outcomes
measure: Cytological tumour response
time frame: Expected (in case of three ePIPAC-OX): 12 weeks
description: Number of patients with positive/negative cytology, based on collected ascites or peritoneal washing cytology during each ePIPAC-OX
measure: Macroscopic tumour response
time frame: Expected (in case of three ePIPAC-OX): 12 weeks
description: Peritoneal Cancer Index and ascites volume during each ePIPAC-OX
measure: Biochemical tumour response
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Tumour marker value measured at baseline, each postoperative day, and four weeks after each ePIPAC-OX
measure: Quality of life: EQ-5D-5L
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: EQ-5D-5L at baseline and one and four weeks after each ePIPAC-OX
measure: Quality of life: QLQ-C30
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: QLQ-C30 at baseline and one and four weeks after each ePIPAC-OX
measure: Quality of life: QLQ-CR29
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: QLQ-CR29 at baseline and one and four weeks after each ePIPAC-OX
measure: Costs
time frame: Expected (in case of three ePIPAC-OX): 16 weeks
description: Costs of treatment, based on questionnaires (iMTA PCQ, iMTA MCQ) four weeks after each ePIPAC-OX, derived from the Dutch costing guidelines for health care research at the time of analysis
measure: Progression-free survival
time frame: 24 months
description: Time between enrolment and clinical, radiological, or macroscopic progression, or death
measure: Overall survival
time frame: 24 months
description: Time between enrolment and death
measure: Environmental safety of ePIPAC-OX
time frame: 1 week (measured only during the first three procedures in the study)
description: Platinum concentrations in the air of the operating room and on the surface of the operating room during ePIPAC-OX
measure: Pharmacokinetics
time frame: Expected (in case of three ePIPAC-OX): 13 weeks
description: Platinum concentrations in plasma and plasma ultrafiltrate (collected before ePIPAC-OX and 5, 10, 20, 30, 60, 120, 240, 360, and 1080 minutes after oxaliplatin injection), urine (collected before ePIPAC-OX and on postoperative days 1, 3, 5, and 7), and two pieces of normal peritoneum and two peritoneal metastases collected during each ePIPAC-OX.
measure: Procedure-related characteristics: intraoperative complications
time frame: Expected (in case of three ePIPAC-OX): 12 weeks
description: Number of procedures with intraoperative complications determined during each ePIPAC-OX
measure: Procedure-related characteristics: adhesions
time frame: Expected (in case of three ePIPAC-OX): 12 weeks
description: Zühlke score determined during each ePIPAC-OX
measure: Procedure-related characteristics: operating time
time frame: Expected (in case of three ePIPAC-OX): 12 weeks
description: Operating time in minutes determined during each ePIPAC-OX
measure: Procedure-related characteristics: blood loss
time frame: Expected (in case of three ePIPAC-OX): 12 weeks
description: Blood loss in minutes determined during each ePIPAC-OX
arm group label: repetitive ePIPAC-OX
arm group type: Experimental
intervention type: Combination Product
intervention name: repetitive ePIPAC-OX
description: Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) (92 mg/m2 body-surface area [BSA]) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four weeks after each procedure, patients undergo clinical, radiological, and biochemical evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease progression, after which standard palliative treatment is (re)considered.
arm group label: repetitive ePIPAC-OX
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Ignace de Hingh, MD, PhD
role: Study Chair
affiliation: Catharina Hospital, Eindhoven, Netherlands
last name: Djamila Boerma, MD, PhD
role: Principal Investigator
affiliation: St Antonius Hospital, Nieuwegein, Netherlands
facility: 
facility: 
country: Netherlands
citation: Giger-Pabst U, Tempfer CB. How to Perform Safe and Technically Optimized Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Experience After a Consecutive Series of 1200 Procedures. J Gastrointest Surg. 2018 Dec;22(12):2187-2193. doi: 10.1007/s11605-018-3916-5. Epub 2018 Aug 21.
PMID: 30132291
citation: Tempfer C, Giger-Pabst U, Hilal Z, Dogan A, Rezniczek GA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer. Arch Gynecol Obstet. 2018 Aug;298(2):243-257. doi: 10.1007/s00404-018-4784-7. Epub 2018 Jun 4.
PMID: 29869089
citation: Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hubner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg. 2017 May;104(6):669-678. doi: 10.1002/bjs.10521.
PMID: 28407227
responsible party type: Sponsor-Investigator
investigator affiliation: Catharina Ziekenhuis Eindhoven
investigator full name: Koen Rovers
investigator title: MD, Coordinating Investigator
mesh term: Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Carcinoma
mesh term: Peritoneal Neoplasms
mesh term: Appendiceal Neoplasms
sharing ipd: Yes
ipd description: Available on request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: End of the study
ipd access criteria: Available on request