<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/NCT03304210</url>
  </required_header>
  <id_info>
    <org_study_id>AGO/2017/003</org_study_id>
    <nct_id>NCT03304210</nct_id>
  </id_info>
  <brief_title>PIPAC Nab-pac for Stomach, Pancreas, Breast and Ovarian Cancer</brief_title>
  <acronym>PIPAC-nabpac</acronym>
  <official_title>Intraperitoneal Aerosolization of Albumin-stabilized Paclitaxel Nanoparticles for Stomach, Pancreas, Breast and Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Ghent</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kom Op Tegen Kanker</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Ghent</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hopital Lariboisière</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Women's Hospital Tübingen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Candiolo Cancer Institute - IRCCS</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centre Hospitalier Universitaire Vaudois</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Ghent</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The PIPAC nab-pac study is designed to examine the maximal tolerated dose of albumin bound&#xD;
      nanoparticle paclitaxel (nab-pac, Abraxane) administered with repeated pressurized&#xD;
      intraperitoneal aerosol chemotherapy (PIPAC), in a multicentre, multinational phase I trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Over 85% of women with ovarian cancer (OC) will develop a peritoneal recurrence after initial&#xD;
      therapy. The prognosis of patients with recurrent disease is poor, with a median survival&#xD;
      ranging from 12 to 24 months. Most of these patients ultimately develop platinum resistant&#xD;
      disease (PROC). Current systemic therapy results in a very modest improvement of progression&#xD;
      free and overall survival. The addition of locoregional, intraperitoneal (IP) therapy may&#xD;
      improve disease control in recurrent OC. Recently, pressurized intraperitoneal aerosol&#xD;
      therapy (PIPAC) was added to the therapeutic arsenal. This novel technique allows repeated&#xD;
      laparoscopy aided aerosol delivery of anticancer drugs to the peritoneal cavity. Abraxane&#xD;
      (nab-pac, Celgene) is a novel 130 nm, albumin-bound (nab) nanoparticle formulation of&#xD;
      paclitaxel which has noteworthy single-agent activity and a favourable toxicity profile when&#xD;
      used systemically in PROC. A recent phase I study showed a significant pharmacokinetic&#xD;
      advantage after IP instillation of nab-pac in patients with peritoneal carcinomatosis from&#xD;
      ovarian or gastro-intestinal (GI) origin.&#xD;
&#xD;
      In phase I of this study, dose escalation will be combined with&#xD;
      pharmacokinetic/pharmacodynamic modelling which incorporates, in addition to plasma, tumour&#xD;
      tissue, and peritoneal drug concentrations, biomarkers of toxicity and efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 16, 2017</start_date>
  <completion_date type="Actual">May 6, 2020</completion_date>
  <primary_completion_date type="Actual">May 6, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximally tolerated dose (MTD) of Abraxane</measure>
    <time_frame>Within 14 weeks of the start of the treatment</time_frame>
    <description>Dose limiting toxicities will be monitored.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Surgical morbidity will be measured</measure>
    <time_frame>6 months after third PIPAC</time_frame>
    <description>This will be estimated with the Dindo-Clavien classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration of Abraxane</measure>
    <time_frame>T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours</time_frame>
    <description>Abraxane will be measured in plasma, using UPLC-MS/MS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under The Curve (AUC) of Abraxane</measure>
    <time_frame>T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours</time_frame>
    <description>Abraxane will be measured in plasma, using LC-MS/MS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics (PD) of Abraxane will be analysed using biomarkers</measure>
    <time_frame>T = 0 weeks, T = 1 week for every PIPAC</time_frame>
    <description>Tumour markers will be analysed - CA15.3 in case of breast cancer, CEA in case of stomach cancer, CA19.9 in case of pancreatic cancer, CA125 in case of ovarian cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics (PD) of Abraxane will be analyzed by tumour biopsies</measure>
    <time_frame>T = 30 minutes</time_frame>
    <description>Tumour samples will be collected (5x5x5 mm³) at the end of the aerosol delivery after each PIPAC procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30)</measure>
    <time_frame>Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC)</time_frame>
    <description>This will be investigated using the EORTC QLQ-C30 questionnaire. As to question 1 to 28: the scale varies from 1 (not at all) to 4 (very much). A higher value indicates a lower quality of life. The total score will be between 28 and 112.&#xD;
The scale of question 29 and 30 varies from 1 (very poor) to 7 (excellent). The higher the value, the better the quality of life. The total score will be between 2 and 14.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (Functional Assessment of Cancer Therapy, FACT-G questionnaire)</measure>
    <time_frame>Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC)</time_frame>
    <description>This will be investigated using the FACT-G questionnaire. The scale of all questions varies from 0 (not at all) to 4 (very much). The total score will be between 0 and 108. The lower the total score, the better the quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutropenia - number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC</time_frame>
    <description>Blood samples will be collected to analyse the absolute neutrophil count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Decreased platelets - number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC</time_frame>
    <description>Blood samples will be collected to analyse the amount of platelets.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Peritoneal Carcinomatosis</condition>
  <condition>Ovarian Cancer Stage IIIB</condition>
  <condition>Ovarian Cancer Stage IIIC</condition>
  <condition>Ovarian Cancer Stage IV</condition>
  <condition>Breast Cancer Stage IIIB</condition>
  <condition>Breast Cancer Stage IIIc</condition>
  <condition>Breast Cancer Stage IV</condition>
  <condition>Stomach Cancer Stage III</condition>
  <condition>Stomach Cancer Stage IV With Metastases</condition>
  <condition>Pancreas Cancer, Stage III</condition>
  <condition>Pancreas Cancer, Stage IV</condition>
  <arm_group>
    <arm_group_label>Abraxane 35 mg/m²</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Abraxane 70 mg/m²</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Abraxane 90 mg/m²</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Abraxane 112.5 mg/m²</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PIPAC with Abraxane (112.5 mg/m²) will be administered every 4 weeks for 3 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Abraxane 140 mg/m²</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PIPAC with Abraxane</intervention_name>
    <description>Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.</description>
    <arm_group_label>Abraxane 112.5 mg/m²</arm_group_label>
    <arm_group_label>Abraxane 140 mg/m²</arm_group_label>
    <arm_group_label>Abraxane 35 mg/m²</arm_group_label>
    <arm_group_label>Abraxane 70 mg/m²</arm_group_label>
    <arm_group_label>Abraxane 90 mg/m²</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Phase I study: patients with advanced carcinomatosis from ovarian, breast, gastric, or&#xD;
             pancreatic origin. No alternative systemic treatment options are available.&#xD;
&#xD;
          -  Age over 18 years&#xD;
&#xD;
          -  Adequate performance status (Karnofsky index &gt; 60%)&#xD;
&#xD;
          -  Absence of intestinal or urinary obstruction&#xD;
&#xD;
          -  Limited size of the majority of peritoneal tumor implants (&lt; 5 mm)&#xD;
&#xD;
          -  Absent or limited ascites&#xD;
&#xD;
          -  Ability to understand the proposed treatment protocol and provide informed consent&#xD;
&#xD;
          -  Expected life expectancy more than 6 months&#xD;
&#xD;
          -  Laboratory data&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 mg/dl or a calculated GFR (CKD-EPI) ≥ 60 mL/min/1.73 m²&#xD;
&#xD;
               -  Serum total bilirubin ≤ 1.5 mg/dl, except for known Gilbert's disease&#xD;
&#xD;
               -  Platelet count &gt; 100.000/µl&#xD;
&#xD;
               -  Hemoglobin &gt; 9g/dl&#xD;
&#xD;
               -  Neutrophil granulocytes &gt; 1.500/ml&#xD;
&#xD;
               -  No major blood coagulation disorders. Parameters within normal range.&#xD;
&#xD;
          -  Absence of alcohol and/or drug abuse&#xD;
&#xD;
          -  No other concurrent malignant disease&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breast feeding. Women who can become pregnant must ensure effective&#xD;
             contraception.&#xD;
&#xD;
          -  Active bacterial, viral or fungal infection&#xD;
&#xD;
          -  Active gastro-duodenal ulcer&#xD;
&#xD;
          -  Parenchymal liver disease (any stage cirrhosis)&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus&#xD;
&#xD;
          -  Psychiatric pathology affecting comprehension and judgement faculty&#xD;
&#xD;
          -  General or local (abdominal) contra-indications for laparoscopic surgery&#xD;
&#xD;
          -  Documented intolerance or allergy to paclitaxel&#xD;
&#xD;
          -  Patients who receive other taxane therapy until three weeks before the first&#xD;
             experimental treatment&#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>Wim P Ceelen, MD, PhD, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Ghent</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UZ Ghent</name>
      <address>
        <city>Ghent</city>
        <state>East-Flanders</state>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Al Rawahi T, Lopes AD, Bristow RE, Bryant A, Elattar A, Chattopadhyay S, Galaal K. Surgical cytoreduction for recurrent epithelial ovarian cancer. Cochrane Database Syst Rev. 2013 Feb 28;2013(2):CD008765. doi: 10.1002/14651858.CD008765.pub3.</citation>
    <PMID>23450588</PMID>
  </reference>
  <reference>
    <citation>Oseledchyk A, Zivanovic O. Intraoperative Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer. Oncology (Williston Park). 2015 Sep;29(9):695-701.</citation>
    <PMID>26384807</PMID>
  </reference>
  <reference>
    <citation>Solass W, Kerb R, Murdter T, Giger-Pabst U, Strumberg D, Tempfer C, Zieren J, Schwab M, Reymond MA. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol. 2014 Feb;21(2):553-9. doi: 10.1245/s10434-013-3213-1. Epub 2013 Sep 5.</citation>
    <PMID>24006094</PMID>
  </reference>
  <reference>
    <citation>Tempfer CB, Rezniczek GA, Ende P, Solass W, Reymond MA. Pressurized Intraperitoneal Aerosol Chemotherapy with Cisplatin and Doxorubicin in Women with Peritoneal Carcinomatosis: A Cohort Study. Anticancer Res. 2015 Dec;35(12):6723-9. doi: 10.1055/s-0035-1560004.</citation>
    <PMID>26637888</PMID>
  </reference>
  <reference>
    <citation>Scheithauer W, Kornek G, Prager G, Stranzl N, Laengle F, Schindl M, Friedl J, Klech J, Roethlin S, Zielinski C. Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. J Gastrointest Oncol. 2016 Apr;7(2):234-8. doi: 10.3978/j.issn.2078-6891.2015.107.</citation>
    <PMID>27034791</PMID>
  </reference>
  <reference>
    <citation>Coleman RL, Brady WE, McMeekin DS, Rose PG, Soper JT, Lentz SS, Hoffman JS, Shahin MS. A phase II evaluation of nanoparticle, albumin-bound (nab) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Jul;122(1):111-5. doi: 10.1016/j.ygyno.2011.03.036. Epub 2011 Apr 15.</citation>
    <PMID>21497382</PMID>
  </reference>
  <reference>
    <citation>Tsai M, Lu Z, Wang J, Yeh TK, Wientjes MG, Au JL. Effects of carrier on disposition and antitumor activity of intraperitoneal Paclitaxel. Pharm Res. 2007 Sep;24(9):1691-701. doi: 10.1007/s11095-007-9298-0. Epub 2007 Apr 20.</citation>
    <PMID>17447121</PMID>
  </reference>
  <reference>
    <citation>Pujade-Lauraine E, Selle F, Weber B, Ray-Coquard IL, Vergote I, Sufliarsky J, Del Campo JM, Lortholary A, Lesoin A, Follana P, Freyer G, Pardo B, Vidal L, Tholander B, Gladieff L, Sassi M, Garin-Chesa P, Nazabadioko S, Marzin K, Pilz K, Joly F. Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study. J Clin Oncol. 2016 Mar 1;34(7):706-13. doi: 10.1200/JCO.2015.62.1474. Epub 2016 Jan 11.</citation>
    <PMID>26755507</PMID>
  </reference>
  <reference>
    <citation>Naumann RW, Coleman RL. Management strategies for recurrent platinum-resistant ovarian cancer. Drugs. 2011 Jul 30;71(11):1397-412. doi: 10.2165/11591720-000000000-00000.</citation>
    <PMID>21812505</PMID>
  </reference>
  <reference>
    <citation>Gradishar WJ. Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother. 2006 Jun;7(8):1041-53. doi: 10.1517/14656566.7.8.1041.</citation>
    <PMID>16722814</PMID>
  </reference>
  <reference>
    <citation>Braeckmans K, Buyens K, Bouquet W, Vervaet C, Joye P, De Vos F, Plawinski L, Doeuvre L, Angles-Cano E, Sanders NN, Demeester J, De Smedt SC. Sizing nanomatter in biological fluids by fluorescence single particle tracking. Nano Lett. 2010 Nov 10;10(11):4435-42. doi: 10.1021/nl103264u. Epub 2010 Oct 5.</citation>
    <PMID>20923181</PMID>
  </reference>
  <reference>
    <citation>Karmali PP, Kotamraju VR, Kastantin M, Black M, Missirlis D, Tirrell M, Ruoslahti E. Targeting of albumin-embedded paclitaxel nanoparticles to tumors. Nanomedicine. 2009 Mar;5(1):73-82. doi: 10.1016/j.nano.2008.07.007. Epub 2008 Oct 1.</citation>
    <PMID>18829396</PMID>
  </reference>
  <reference>
    <citation>Cheung YK, Chappell R. Sequential designs for phase I clinical trials with late-onset toxicities. Biometrics. 2000 Dec;56(4):1177-82. doi: 10.1111/j.0006-341x.2000.01177.x.</citation>
    <PMID>11129476</PMID>
  </reference>
  <reference>
    <citation>Colin P, De Smet L, De Bock L, Goeteyn W, Boussery K, Vervaet C, Van Bocxlaer J. Enzymatic tumour tissue digestion coupled to SPE-UPLC-Tandem Mass Spectrometry as a tool to explore paclitaxel tumour penetration. Talanta. 2014 Nov;129:119-25. doi: 10.1016/j.talanta.2014.05.028. Epub 2014 May 24.</citation>
    <PMID>25127573</PMID>
  </reference>
  <reference>
    <citation>Colin P, De Smet L, Vervaet C, Remon JP, Ceelen W, Van Bocxlaer J, Boussery K, Vermeulen A. A model based analysis of IPEC dosing of paclitaxel in rats. Pharm Res. 2014 Oct;31(10):2876-86. doi: 10.1007/s11095-014-1384-5. Epub 2014 May 22.</citation>
    <PMID>24848338</PMID>
  </reference>
  <reference>
    <citation>Friedlander ML, King MT. Patient-reported outcomes in ovarian cancer clinical trials. Ann Oncol. 2013 Dec;24 Suppl 10:x64-x68. doi: 10.1093/annonc/mdt474.</citation>
    <PMID>24265408</PMID>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>September 11, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>August 3, 2020</last_update_submitted>
  <last_update_submitted_qc>August 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PIPAC</keyword>
  <keyword>Peritoneal carcinomatosis</keyword>
  <keyword>Ovarian cancer</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Pharmacodynamics</keyword>
  <keyword>Safety and efficacy</keyword>
  <keyword>Abraxane</keyword>
  <keyword>Breast cancer</keyword>
  <keyword>Pancreas cancer</keyword>
  <keyword>Stomach cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Peritoneal Neoplasms</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Hereditary Breast and Ovarian Cancer Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>January 10, 2022</submitted>
    <returned>March 11, 2022</returned>
    <submitted>January 20, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03304210
org study id: AGO/2017/003
nct id: NCT03304210
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The PIPAC nab-pac study is designed to examine the maximal tolerated dose of albumin bound
      nanoparticle paclitaxel (nab-pac, Abraxane) administered with repeated pressurized
      intraperitoneal aerosol chemotherapy (PIPAC), in a multicentre, multinational phase I trial.
Over 85% of women with ovarian cancer (OC) will develop a peritoneal recurrence after initial
      therapy. The prognosis of patients with recurrent disease is poor, with a median survival
      ranging from 12 to 24 months. Most of these patients ultimately develop platinum resistant
      disease (PROC). Current systemic therapy results in a very modest improvement of progression
      free and overall survival. The addition of locoregional, intraperitoneal (IP) therapy may
      improve disease control in recurrent OC. Recently, pressurized intraperitoneal aerosol
      therapy (PIPAC) was added to the therapeutic arsenal. This novel technique allows repeated
      laparoscopy aided aerosol delivery of anticancer drugs to the peritoneal cavity. Abraxane
      (nab-pac, Celgene) is a novel 130 nm, albumin-bound (nab) nanoparticle formulation of
      paclitaxel which has noteworthy single-agent activity and a favourable toxicity profile when
      used systemically in PROC. A recent phase I study showed a significant pharmacokinetic
      advantage after IP instillation of nab-pac in patients with peritoneal carcinomatosis from
      ovarian or gastro-intestinal (GI) origin.

      In phase I of this study, dose escalation will be combined with
      pharmacokinetic/pharmacodynamic modelling which incorporates, in addition to plasma, tumour
      tissue, and peritoneal drug concentrations, biomarkers of toxicity and efficacy.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Maximally tolerated dose (MTD) of Abraxane
time frame: Within 14 weeks of the start of the treatment
description: Dose limiting toxicities will be monitored.
measure: Surgical morbidity will be measured
time frame: 6 months after third PIPAC
description: This will be estimated with the Dindo-Clavien classification
measure: Maximum plasma concentration of Abraxane
time frame: T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours
description: Abraxane will be measured in plasma, using UPLC-MS/MS.
measure: Area Under The Curve (AUC) of Abraxane
time frame: T = 0 minutes, T = 15 minutes, T = 30 minutes, T = 60 minutes, T = 1.5 hour, T = 2 hours, T = 4 hours, T = 8 hours, T = 12 hours, T = 24 hours
description: Abraxane will be measured in plasma, using LC-MS/MS.
measure: Pharmacodynamics (PD) of Abraxane will be analysed using biomarkers
time frame: T = 0 weeks, T = 1 week for every PIPAC
description: Tumour markers will be analysed - CA15.3 in case of breast cancer, CEA in case of stomach cancer, CA19.9 in case of pancreatic cancer, CA125 in case of ovarian cancer.
measure: Pharmacodynamics (PD) of Abraxane will be analyzed by tumour biopsies
time frame: T = 30 minutes
description: Tumour samples will be collected (5x5x5 mm³) at the end of the aerosol delivery after each PIPAC procedure.
measure: Quality of Life (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30)
time frame: Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC)
description: This will be investigated using the EORTC QLQ-C30 questionnaire. As to question 1 to 28: the scale varies from 1 (not at all) to 4 (very much). A higher value indicates a lower quality of life. The total score will be between 28 and 112.
The scale of question 29 and 30 varies from 1 (very poor) to 7 (excellent). The higher the value, the better the quality of life. The total score will be between 2 and 14.
measure: Quality of Life (Functional Assessment of Cancer Therapy, FACT-G questionnaire)
time frame: Pre-operatively (every PIPAC), week 2 (every PIPAC) and, month 2 and month 6 (after the third PIPAC)
description: This will be investigated using the FACT-G questionnaire. The scale of all questions varies from 0 (not at all) to 4 (very much). The total score will be between 0 and 108. The lower the total score, the better the quality of life.
measure: Neutropenia - number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
description: Blood samples will be collected to analyse the absolute neutrophil count
measure: Decreased platelets - number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: Pre-operatively, and 12 hours, 24 hours and 1 week after each PIPAC
description: Blood samples will be collected to analyse the amount of platelets.
arm group label: Abraxane 35 mg/m²
arm group type: Experimental
description: PIPAC with Abraxane (35 mg/m²) will be administered every 4 weeks for 3 cycles.
arm group label: Abraxane 70 mg/m²
arm group type: Experimental
description: PIPAC with Abraxane (70 mg/m²) will be administered every 4 weeks for 3 cycles.
arm group label: Abraxane 90 mg/m²
arm group type: Experimental
description: PIPAC with Abraxane (90 mg/m²) will be administered every 4 weeks for 3 cycles.
arm group label: Abraxane 112.5 mg/m²
arm group type: Experimental
description: PIPAC with Abraxane (112.5 mg/m²) will be administered every 4 weeks for 3 cycles.
arm group label: Abraxane 140 mg/m²
arm group type: Experimental
description: PIPAC with Abraxane (140 mg/m²) will be administered every 4 weeks for 3 cycles.
intervention type: Drug
intervention name: PIPAC with Abraxane
description: Albumin bound nanoparticle paclitaxel (Abraxane) will be administered intraperitoneally using the PIPAC technique. The administered dose will escalate ranging from 35 to 140 mg/m². PIPAC will be performed every 4 weeks for 3 cycles.
arm group label: Abraxane 112.5 mg/m²
arm group label: Abraxane 140 mg/m²
arm group label: Abraxane 35 mg/m²
arm group label: Abraxane 70 mg/m²
arm group label: Abraxane 90 mg/m²
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wim P Ceelen, MD, PhD, Prof
role: Principal Investigator
affiliation: University Hospital, Ghent
facility: 
country: Belgium
citation: Al Rawahi T, Lopes AD, Bristow RE, Bryant A, Elattar A, Chattopadhyay S, Galaal K. Surgical cytoreduction for recurrent epithelial ovarian cancer. Cochrane Database Syst Rev. 2013 Feb 28;2013(2):CD008765. doi: 10.1002/14651858.CD008765.pub3.
PMID: 23450588
citation: Oseledchyk A, Zivanovic O. Intraoperative Hyperthermic Intraperitoneal Chemotherapy in Patients With Advanced Ovarian Cancer. Oncology (Williston Park). 2015 Sep;29(9):695-701.
PMID: 26384807
citation: Solass W, Kerb R, Murdter T, Giger-Pabst U, Strumberg D, Tempfer C, Zieren J, Schwab M, Reymond MA. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol. 2014 Feb;21(2):553-9. doi: 10.1245/s10434-013-3213-1. Epub 2013 Sep 5.
PMID: 24006094
citation: Tempfer CB, Rezniczek GA, Ende P, Solass W, Reymond MA. Pressurized Intraperitoneal Aerosol Chemotherapy with Cisplatin and Doxorubicin in Women with Peritoneal Carcinomatosis: A Cohort Study. Anticancer Res. 2015 Dec;35(12):6723-9. doi: 10.1055/s-0035-1560004.
PMID: 26637888
citation: Scheithauer W, Kornek G, Prager G, Stranzl N, Laengle F, Schindl M, Friedl J, Klech J, Roethlin S, Zielinski C. Phase II trial of capecitabine plus nab-paclitaxel in patients with metastatic pancreatic adenocarcinoma. J Gastrointest Oncol. 2016 Apr;7(2):234-8. doi: 10.3978/j.issn.2078-6891.2015.107.
PMID: 27034791
citation: Coleman RL, Brady WE, McMeekin DS, Rose PG, Soper JT, Lentz SS, Hoffman JS, Shahin MS. A phase II evaluation of nanoparticle, albumin-bound (nab) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Jul;122(1):111-5. doi: 10.1016/j.ygyno.2011.03.036. Epub 2011 Apr 15.
PMID: 21497382
citation: Tsai M, Lu Z, Wang J, Yeh TK, Wientjes MG, Au JL. Effects of carrier on disposition and antitumor activity of intraperitoneal Paclitaxel. Pharm Res. 2007 Sep;24(9):1691-701. doi: 10.1007/s11095-007-9298-0. Epub 2007 Apr 20.
PMID: 17447121
citation: Pujade-Lauraine E, Selle F, Weber B, Ray-Coquard IL, Vergote I, Sufliarsky J, Del Campo JM, Lortholary A, Lesoin A, Follana P, Freyer G, Pardo B, Vidal L, Tholander B, Gladieff L, Sassi M, Garin-Chesa P, Nazabadioko S, Marzin K, Pilz K, Joly F. Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study. J Clin Oncol. 2016 Mar 1;34(7):706-13. doi: 10.1200/JCO.2015.62.1474. Epub 2016 Jan 11.
PMID: 26755507
citation: Naumann RW, Coleman RL. Management strategies for recurrent platinum-resistant ovarian cancer. Drugs. 2011 Jul 30;71(11):1397-412. doi: 10.2165/11591720-000000000-00000.
PMID: 21812505
citation: Gradishar WJ. Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother. 2006 Jun;7(8):1041-53. doi: 10.1517/14656566.7.8.1041.
PMID: 16722814
citation: Braeckmans K, Buyens K, Bouquet W, Vervaet C, Joye P, De Vos F, Plawinski L, Doeuvre L, Angles-Cano E, Sanders NN, Demeester J, De Smedt SC. Sizing nanomatter in biological fluids by fluorescence single particle tracking. Nano Lett. 2010 Nov 10;10(11):4435-42. doi: 10.1021/nl103264u. Epub 2010 Oct 5.
PMID: 20923181
citation: Karmali PP, Kotamraju VR, Kastantin M, Black M, Missirlis D, Tirrell M, Ruoslahti E. Targeting of albumin-embedded paclitaxel nanoparticles to tumors. Nanomedicine. 2009 Mar;5(1):73-82. doi: 10.1016/j.nano.2008.07.007. Epub 2008 Oct 1.
PMID: 18829396
citation: Cheung YK, Chappell R. Sequential designs for phase I clinical trials with late-onset toxicities. Biometrics. 2000 Dec;56(4):1177-82. doi: 10.1111/j.0006-341x.2000.01177.x.
PMID: 11129476
citation: Colin P, De Smet L, De Bock L, Goeteyn W, Boussery K, Vervaet C, Van Bocxlaer J. Enzymatic tumour tissue digestion coupled to SPE-UPLC-Tandem Mass Spectrometry as a tool to explore paclitaxel tumour penetration. Talanta. 2014 Nov;129:119-25. doi: 10.1016/j.talanta.2014.05.028. Epub 2014 May 24.
PMID: 25127573
citation: Colin P, De Smet L, Vervaet C, Remon JP, Ceelen W, Van Bocxlaer J, Boussery K, Vermeulen A. A model based analysis of IPEC dosing of paclitaxel in rats. Pharm Res. 2014 Oct;31(10):2876-86. doi: 10.1007/s11095-014-1384-5. Epub 2014 May 22.
PMID: 24848338
citation: Friedlander ML, King MT. Patient-reported outcomes in ovarian cancer clinical trials. Ann Oncol. 2013 Dec;24 Suppl 10:x64-x68. doi: 10.1093/annonc/mdt474.
PMID: 24265408
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Pancreatic Neoplasms
mesh term: Carcinoma
mesh term: Peritoneal Neoplasms
mesh term: Stomach Neoplasms
mesh term: Hereditary Breast and Ovarian Cancer Syndrome
mesh term: Albumin-Bound Paclitaxel
submitted: January 10, 2022
returned: March 11, 2022
submitted: January 20, 2023