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  • Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II…

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Oncology
Protocol
Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC)
  1. Koen P Rovers1,
  2. Robin J Lurvink1,
  3. Emma CE Wassenaar2,
  4. Thomas JM Kootstra2,
  5. Harm J Scholten3,
  6. Rudaba Tajzai4,
  7. Maarten J Deenen4,
  8. Joost Nederend5,
  9. Max J Lahaye6,
  10. Clément JR Huysentruyt7,
  11. Iris van ’t Erve8,
  12. Remond JA Fijneman8,
  13. Alexander Constantinides9,
  14. Onno Kranenburg9,
  15. Maartje Los10,
  16. Anna MJ Thijs11,
  17. Geert-Jan M Creemers11,
  18. Jacobus WA Burger1,
  19. Marinus J Wiezer2,
  20. Djamila Boerma2,
  21. Simon W Nienhuijs1,
  22. Ignace HJT de Hingh1,12
  1. 1 Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
  2. 2 Department of Surgery, Sint Antonius Hospital, Nieuwegein, The Netherlands
  3. 3 Department of Anaesthesiology, Catharina Hospital, Eindhoven, The Netherlands
  4. 4 Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, The Netherlands
  5. 5 Department of Radiology, Catharina Hospital, Eindhoven, The Netherlands
  6. 6 Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
  7. 7 Department of Pathology, Catharina Hospital, Eindhoven, The Netherlands
  8. 8 Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
  9. 9 Imaging and Cancer, UMC Utrecht, Utrecht, The Netherlands
  10. 10 Department of Medical Oncology, Sint Antonius Hospital, Nieuwegein, The Netherlands
  11. 11 Department of Medical Oncology, Catharina Hospital, Eindhoven, The Netherlands
  12. 12 GROW - School for Oncology and Development Biology, Maastricht University, Maastricht, Netherlands
  1. Correspondence to Professor Ignace HJT de Hingh; ignace.d.hingh{at}catharinaziekenhuis.nl

Abstract

Introduction 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. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy.

Methods and analysis This multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. 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 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. 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 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response.

Ethics and dissemination This study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders.

Trial registration number NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.

  • peritoneal metastases
  • colorectal cancer
  • colorectal surgery
  • gastrointestinal tumours
  • intraperitoneal chemotherapy
  • PIPAC

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2019-030408

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    Footnotes

    • Contributors KR is the coordinating investigator. RL, AT, GC, JB and SN are the local investigators of the first study centre. EW, TK, ML, MW and DB are the local investigators of the second study centre. RT performs the pharmacokinetic analyses. MD is the study pharmacologist supervising the pharmacokinetic analyses. JN and MJL are the study radiologists performing the central radiological review. CH is the study pathologist performing the central histopathological review. HS is the study anaesthesiologist who developed the protocols for perioperative care. IE and RF are responsible for translational research on blood. AC and OK are responsible for translational research on ascites and PM. IH is the principal investigator. KR, RL and IH made substantial contributions to conception and design of the study, drafted the protocol and drafted the manuscript. EW, TK, HS, RT, MD, JN, MJL, CH, IE, RF, AC, OK, ML, AT, GC, JB, MW, DB and SN made substantial contributions to conception and design of the study and critically revised the protocol and the manuscript for important intellectual content. KR, RL, EW, TK, HS, RT, MD, JN, MJL, CH, IE, RF, AC, OK, ML, AT, GC, JB, MW, DB, SN and IH gave final approval of the version to be published and agree to be accountable for all aspects of the work.

    • Funding This study is supported by Catharina Research Foundation (grant number: 2017-5) and St. Antonius Research Foundation (grant number: 17.4).

    • Competing interests None declared.

    • Ethics approval This study is approved by an ethics committee (MEC-U, Nieuwegein, The Netherlands, number R17.038), the Dutch competent authority (CCMO, The Hague, The Netherlands, number NL60405.100.17) and the institutional review boards of Catharina Hospital (Lokale Uitvoerbaarheidscommissie, number CZE-2017.50) and St. Antonius Hospital (R&D, number L18.021) .

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Patient consent for publication Not required.