<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/NCT03294252</url>
  </required_header>
  <id_info>
    <org_study_id>ICO-N-2016-03</org_study_id>
    <nct_id>NCT03294252</nct_id>
  </id_info>
  <brief_title>Oxaliplatin in PIPAC for Nonresectable Peritoneal Metastases of Digestive Cancers</brief_title>
  <acronym>PIPOX</acronym>
  <official_title>Phase I / II Dose Escalation of Oxaliplatin Via a Laparoscopic Approach of Aerosol Pressurized Intraperitoneal Chemotherapy for Nonresectable Peritoneal Metastases of Digestive Cancers (Stomach, Hail and Colorectal)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Cancerologie de l'Ouest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut Cancerologie de l'Ouest</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Current curative treatment of digestive peritoneal carcinomatosis consists of complete&#xD;
      cytoreduction surgery associated with intraperitoneal chemotherapy. This treatment has&#xD;
      important limits: a high morbimortality and the impossibility of repeating the sessions. The&#xD;
      majority of patients are therefore treated with systemic chemotherapy, which despite its&#xD;
      progress, remains palliative.&#xD;
&#xD;
      Pressurized Intraperitoneal aerosol chemotherapy (PIPAC) has many advantages: under&#xD;
      laparoscopy, low morbidity, good intratumoral penetration of cytotoxics, possibility of&#xD;
      repeating the sessions and low financial cost.&#xD;
&#xD;
      Therefore, the investigator propose a phase 1 study, in colorectal and stomach cancer, with&#xD;
      oxaliplatin doses escalation in Pressurized Intraperitoneal aerosol chemotherapy. It would&#xD;
      allow a better tumor response, with potentially few risks and thus improve survival in&#xD;
      patients with digestive peritoneal carcinoses, increasing access to cytoreductive surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this study is to determine the maximum tolerated dose (mtd) of oxaliplatin&#xD;
      to be used during PIPAC.&#xD;
&#xD;
      Study design is a phase I/II, multicentre, non-comparative, non-randomised dose escalation&#xD;
      clinical trial.&#xD;
&#xD;
      The phase I study will consist of a 3 by 3 dose escalation according to modified fibonacci&#xD;
      dose escalation, starting at the current PIPAC dose (i.e. 90mg/m2), up to a maximum dose of&#xD;
      300mg/m2, corresponding to the current Intraperitoneal chemohyperthermia.&#xD;
&#xD;
      Each patient may receive up to 5 PIPAC sessions ; DLT period will be from the first day (D1)&#xD;
      of the first PIPAC session until the end of the second PIPAC session, including the interval&#xD;
      chemotherapy (i.e. D-1 of the 3rd CIPPA session), i.e. 4 to 6 weeks later ; Phase II study is&#xD;
      an extension cohort at the recommended dose determined in the Phase I study. It will be a&#xD;
      multi-centre, single-arm study and will analyse overall patient survival and secondary&#xD;
      resectability rates with complete cytoreductive surgery and intraperitoneal&#xD;
      chemohyperthermia. It will be conducted in approximately 20 patients treated at the&#xD;
      recommended dose and followed for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The 34 patients included had all completed their treatment period under the protocol and the&#xD;
    data could be collected to assess the main objective and the secondary objectives before the&#xD;
    last theoretical follow-up.&#xD;
  </why_stopped>
  <start_date type="Actual">May 24, 2017</start_date>
  <completion_date type="Actual">October 1, 2021</completion_date>
  <primary_completion_date type="Actual">February 5, 2019</primary_completion_date>
  <phase>Phase 1/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>Maximal Tolerated Dose</measure>
    <time_frame>8 to 12 weeks</time_frame>
    <description>Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommanded dose for the extension phase</measure>
    <time_frame>8 to 12 weeks</time_frame>
    <description>Dose level below the maximum tolerated dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative toxicity after the end of the PIPAC sessions received (maximum 5) at the same dose level</measure>
    <time_frame>24 months after the last PIPAC received</time_frame>
    <description>with CTC-AE scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>24 months after the last PIPAC received</time_frame>
    <description>Median overall survival at the end of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>12 months after the last PIPAC received</time_frame>
    <description>Median PFS, time between the first PIPAC received and progression or death in absence of progression</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Digestive Cancer</condition>
  <arm_group>
    <arm_group_label>Oxaliplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The experimental drugs used in this protocol are Oxaliplatin, 5-Fluorouracil and L-Folinic acid. All are used as part of their marketing authorization, with the exception of Oxaliplatin as regards its mode of administration specific to the PIPAC procedure (injection and nebulisation in intraperitoneal).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-Fluorouracil</intervention_name>
    <description>Presentation: Concentrated solution for concentrated infusion in vials containing 250 mg, 500 mg, 1 g and 5 g, in 5 ml, 10 ml, 20 ml and 100 ml respectively, providing a 50 mg / ml solution. Dosage: 400mg / m2. Administration: IV. Day of administration: between 1 h and 24 h before PIPAC.</description>
    <arm_group_label>Oxaliplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>L-Folinic acid</intervention_name>
    <description>Presentation: lyophilisate for parenteral use, dosed at 25 mg, and in the form of a solution for injection by IM or IV dosed at 25 mg / 2.5 ml. Dosage: 20mg / m2. Administration: IV. Day of administration: between 1 h and 24 h before PIPAC.</description>
    <arm_group_label>Oxaliplatin</arm_group_label>
    <other_name>ELVORIN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Concentrated solution for infusion dosed with 50 mg and 100 mg. Dosage: depending on the dose range assigned to inclusion (from 90mg / m2 to 300mg / m2). Administration: the solution is packaged in a syringe which is subsequently used for injection and not in a conventional bag. The product is administered in a high-pressure injector, during the PIPAC. Day of administration : J1 of PIPAC</description>
    <arm_group_label>Oxaliplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. Patient age ≥ 18 years 2. Histological or cytological diagnosis or suspicion of&#xD;
        peritoneal carcinosis of colorectal, gastric or bowel origin 3. Having previously received&#xD;
        at least 3 months of systemic chemotherapy for metastatic disease (type of chemotherapy&#xD;
        left to the discretion of each investigator). Patients who received bevacizumab (Avastin®)&#xD;
        can be included if and only if the time between the last treatment administered and the&#xD;
        first PIPAC received is at least 4 weeks 4. ECOG performance index &lt; or = 2 5. Life&#xD;
        expectancy&gt; 3 months 6. Peripheral neuropathy grade ≤ 1 7. Hematological function:&#xD;
        Hemoglobin ≥ 9 g / dL, leukocytes ≥ 4000 / mm3, PNN ≥ 1500 / mm3, platelets ≥ 100 000 / mm3&#xD;
        8. Creatinine clearance&gt; 50 mL / min (cockcroft and Gault formula) 9. Hepatic function:&#xD;
        Total bilirubin ≤ 1.5 x ULN, ASAT and ALAT ≤ 3 x ULN, Alkaline phosphatases ≤ 3 x ULN 10 .&#xD;
        Patients with no known or partial deficiency of Dihydropyrimidine dehydrogenase (i.e. DPD)&#xD;
        11. Effective contraception for women of childbearing age 13. Informing the patient and&#xD;
        obtaining free, informed and written consent signed by the patient and his / her&#xD;
        investigator.&#xD;
&#xD;
        14. Affiliated subject or beneficiary of the social security scheme.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who received bevacizumab (Avastin®) less than 4 weeks ago can not be included&#xD;
&#xD;
          2. Extra-peritoneal metastases, except for less than 3 pulmonary nodules (each size &lt;5mm)&#xD;
&#xD;
          3. Known hypersensitivity to Oxaliplatin&#xD;
&#xD;
          4. Known complete dihydropyrimidine dehydrogenase (i.e. DPD) deficiency&#xD;
&#xD;
          5. Peripheral neuropathy Grade &gt;1 due to or not with Oxaliplatin previously used&#xD;
&#xD;
          6. Active or other serious underlying disease that may prevent the patient from receiving&#xD;
             treatment&#xD;
&#xD;
          7. Intracranial or intraocular hypertension (ongoing at the time of inclusion)&#xD;
&#xD;
          8. Severe or Severe Heart Failure (ongoing at the time of inclusion)&#xD;
&#xD;
          9. Complete intestinal obstruction (ongoing at the time of inclusion)&#xD;
&#xD;
         10. Other concurrent cancer or history of cancer other than in situ cancer of treated&#xD;
             cervix or basal cell carcinoma or squamous cell carcinoma&#xD;
&#xD;
         11. Pregnant or nursing women&#xD;
&#xD;
         12. Persons deprived of their liberty or under guardianship or unable to give their&#xD;
             consent&#xD;
&#xD;
         13. Inability to submit to medical follow-up of the trial for geographical, social or&#xD;
             psychological reasons&#xD;
&#xD;
         14. Long-term corticosteroids (duration&gt; 3 months), except for weaning for at least 3&#xD;
             months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>DUMONT Frederic, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut de Cancérologie de l'Ouest</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO René Gauducheau</name>
      <address>
        <city>Saint-Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Begin</name>
      <address>
        <city>Saint-Mandé</city>
        <zip>94163</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <last_update_submitted>April 19, 2022</last_update_submitted>
  <last_update_submitted_qc>April 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PIPAC</keyword>
  <keyword>oxaliplatin</keyword>
  <keyword>peritoneal metastases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Gastrointestinal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Folic Acid</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_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/NCT03294252
org study id: ICO-N-2016-03
nct id: NCT03294252
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Current curative treatment of digestive peritoneal carcinomatosis consists of complete
      cytoreduction surgery associated with intraperitoneal chemotherapy. This treatment has
      important limits: a high morbimortality and the impossibility of repeating the sessions. The
      majority of patients are therefore treated with systemic chemotherapy, which despite its
      progress, remains palliative.

      Pressurized Intraperitoneal aerosol chemotherapy (PIPAC) has many advantages: under
      laparoscopy, low morbidity, good intratumoral penetration of cytotoxics, possibility of
      repeating the sessions and low financial cost.

      Therefore, the investigator propose a phase 1 study, in colorectal and stomach cancer, with
      oxaliplatin doses escalation in Pressurized Intraperitoneal aerosol chemotherapy. It would
      allow a better tumor response, with potentially few risks and thus improve survival in
      patients with digestive peritoneal carcinoses, increasing access to cytoreductive surgery.
The objective of this study is to determine the maximum tolerated dose (mtd) of oxaliplatin
      to be used during PIPAC.

      Study design is a phase I/II, multicentre, non-comparative, non-randomised dose escalation
      clinical trial.

      The phase I study will consist of a 3 by 3 dose escalation according to modified fibonacci
      dose escalation, starting at the current PIPAC dose (i.e. 90mg/m2), up to a maximum dose of
      300mg/m2, corresponding to the current Intraperitoneal chemohyperthermia.

      Each patient may receive up to 5 PIPAC sessions ; DLT period will be from the first day (D1)
      of the first PIPAC session until the end of the second PIPAC session, including the interval
      chemotherapy (i.e. D-1 of the 3rd CIPPA session), i.e. 4 to 6 weeks later ; Phase II study is
      an extension cohort at the recommended dose determined in the Phase I study. It will be a
      multi-centre, single-arm study and will analyse overall patient survival and secondary
      resectability rates with complete cytoreductive surgery and intraperitoneal
      chemohyperthermia. It will be conducted in approximately 20 patients treated at the
      recommended dose and followed for 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximal Tolerated Dose
time frame: 8 to 12 weeks
description: Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)
measure: Recommanded dose for the extension phase
time frame: 8 to 12 weeks
description: Dose level below the maximum tolerated dose
measure: Cumulative toxicity after the end of the PIPAC sessions received (maximum 5) at the same dose level
time frame: 24 months after the last PIPAC received
description: with CTC-AE scale
measure: Overall survival
time frame: 24 months after the last PIPAC received
description: Median overall survival at the end of the study
measure: Progression-Free Survival
time frame: 12 months after the last PIPAC received
description: Median PFS, time between the first PIPAC received and progression or death in absence of progression
arm group label: Oxaliplatin
arm group type: Experimental
description: The experimental drugs used in this protocol are Oxaliplatin, 5-Fluorouracil and L-Folinic acid. All are used as part of their marketing authorization, with the exception of Oxaliplatin as regards its mode of administration specific to the PIPAC procedure (injection and nebulisation in intraperitoneal).
intervention type: Drug
intervention name: 5-Fluorouracil
description: Presentation: Concentrated solution for concentrated infusion in vials containing 250 mg, 500 mg, 1 g and 5 g, in 5 ml, 10 ml, 20 ml and 100 ml respectively, providing a 50 mg / ml solution. Dosage: 400mg / m2. Administration: IV. Day of administration: between 1 h and 24 h before PIPAC.
arm group label: Oxaliplatin
intervention type: Drug
intervention name: L-Folinic acid
description: Presentation: lyophilisate for parenteral use, dosed at 25 mg, and in the form of a solution for injection by IM or IV dosed at 25 mg / 2.5 ml. Dosage: 20mg / m2. Administration: IV. Day of administration: between 1 h and 24 h before PIPAC.
arm group label: Oxaliplatin
other name: ELVORIN
intervention type: Drug
intervention name: Oxaliplatin
description: Concentrated solution for infusion dosed with 50 mg and 100 mg. Dosage: depending on the dose range assigned to inclusion (from 90mg / m2 to 300mg / m2). Administration: the solution is packaged in a syringe which is subsequently used for injection and not in a conventional bag. The product is administered in a high-pressure injector, during the PIPAC. Day of administration : J1 of PIPAC
arm group label: Oxaliplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: DUMONT Frederic, MD
role: Principal Investigator
affiliation: Institut de Cancérologie de l'Ouest
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Gastrointestinal Neoplasms
mesh term: Leucovorin
mesh term: Folic Acid
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Levoleucovorin