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PIPAC for Peritoneal Metastases of Colorectal Cancer (CRC-PIPAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03246321
Recruitment Status : Completed
First Posted : August 11, 2017
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
Koen Rovers, Catharina Ziekenhuis Eindhoven

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Peritoneal Neoplasms Appendiceal Neoplasms Peritoneal Carcinomatosis Combination Product: repetitive ePIPAC-OX Phase 2

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 1, 2017
Actual Primary Completion Date : October 1, 2019
Actual Study Completion Date : October 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oxaliplatin

Arm Intervention/treatment
Experimental: repetitive ePIPAC-OX Combination Product: repetitive ePIPAC-OX
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.




Primary Outcome Measures :
  1. Major toxicity [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    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


Secondary Outcome Measures :
  1. Minor toxicity [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade II, up to 4 weeks after the last ePIPAC-OX

  2. Organ-specific toxicity [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    Number of patients that develops bone marrow, kidney, or liver function disorders, up to four weeks after the last ePIPAC-OX

  3. Major postoperative complications [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    Number of patients with Clavien-Dindo grade III-V postoperative complications, up to four weeks after the last ePIPAC

  4. Minor postoperative complications [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    Number of patients with Clavien-Dindo grade II postoperative complications, up to four weeks after the last ePIPAC-OX

  5. Hospital stay [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    Number of days between ePIPAC-OX and initial discharge, up to four weeks after the last ePIPAC-OX

  6. Readmissions [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    Number of hospital admissions after initial discharge after ePIPAC-OX, up to four weeks after the last ePIPAC-OX

  7. Radiological tumour response [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    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)

  8. Histopathological tumour response [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    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

  9. Cytological tumour response [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Number of patients with positive/negative cytology, based on collected ascites or peritoneal washing cytology during each ePIPAC-OX

  10. Macroscopic tumour response [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Peritoneal Cancer Index and ascites volume during each ePIPAC-OX

  11. Biochemical tumour response [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    Tumour marker value measured at baseline, each postoperative day, and four weeks after each ePIPAC-OX

  12. Quality of life: EQ-5D-5L [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    EQ-5D-5L at baseline and one and four weeks after each ePIPAC-OX

  13. Quality of life: QLQ-C30 [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    QLQ-C30 at baseline and one and four weeks after each ePIPAC-OX

  14. Quality of life: QLQ-CR29 [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    QLQ-CR29 at baseline and one and four weeks after each ePIPAC-OX

  15. Costs [ Time Frame: Expected (in case of three ePIPAC-OX): 16 weeks ]
    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

  16. Progression-free survival [ Time Frame: 24 months ]
    Time between enrolment and clinical, radiological, or macroscopic progression, or death

  17. Overall survival [ Time Frame: 24 months ]
    Time between enrolment and death

  18. Environmental safety of ePIPAC-OX [ Time Frame: 1 week (measured only during the first three procedures in the study) ]
    Platinum concentrations in the air of the operating room and on the surface of the operating room during ePIPAC-OX

  19. Pharmacokinetics [ Time Frame: Expected (in case of three ePIPAC-OX): 13 weeks ]
    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.

  20. Procedure-related characteristics: intraoperative complications [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Number of procedures with intraoperative complications determined during each ePIPAC-OX

  21. Procedure-related characteristics: adhesions [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Zühlke score determined during each ePIPAC-OX

  22. Procedure-related characteristics: operating time [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Operating time in minutes determined during each ePIPAC-OX

  23. Procedure-related characteristics: blood loss [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Blood loss in minutes determined during each ePIPAC-OX



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Eligible patients are adults who have:

  • a World Health Organisation (WHO) performance status of ≤1;
  • histological or cytological proof of PM of a colorectal or appendiceal carcinoma;
  • unresectable disease determined by abdominal computed tomography (CT) and a diagnostic laparoscopy or laparotomy;
  • adequate organ functions (haemoglobin ≥5.0 mmol/L, neutrophils ≥1.5 x 109/L, platelets ≥100 x 109/L, serum creatinine <1.5 x ULN, creatinine clearance ≥30 ml/min, and liver transaminases <5 x ULN);
  • no symptoms of gastrointestinal obstruction;
  • no radiological evidence of systemic metastases;
  • no contraindications for oxaliplatin or 5-fluorouracil/leucovorin;
  • no contraindications for a laparoscopy;
  • no previous PIPAC-procedures.

Enrolled patients are excluded from the analyses in case they did not receive a first ePIPAC-OX, e.g.:

  • due to systemic metastases on baseline thoracoabdominal CT, or;
  • due to non-access during first ePIPAC-OX, or;
  • due to resectable disease during first ePIPAC-OX.

Importantly, enrolment is allowed for patients with an unresected primary tumour (if asymptomatic) and for patients in various lines of palliative treatment, including patients who refuse, have not had, or do not qualify for first-line palliative systemic therapy. All potentially eligible patients are discussed by a multidisciplinary team. Enrolled patients are informed about the potential consequences of postponing or discontinuing standard palliative treatment by a medical oncologist prior to enrolment.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03246321


Locations
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Netherlands
Catharina Hospital
Eindhoven, Netherlands
St. Antonius Hospital
Nieuwegein, Netherlands
Sponsors and Collaborators
Koen Rovers
Investigators
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Study Chair: Ignace de Hingh, MD, PhD Catharina Hospital, Eindhoven, Netherlands
Principal Investigator: Djamila Boerma, MD, PhD St Antonius Hospital, Nieuwegein, Netherlands

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Koen Rovers, MD, Coordinating Investigator, Catharina Ziekenhuis Eindhoven
ClinicalTrials.gov Identifier: NCT03246321     History of Changes
Other Study ID Numbers: NL60405.100.17
2017-000927-29 ( EudraCT Number )
NTR6603 ( Registry Identifier: NTR )
ISRCTN89947480 ( Registry Identifier: ISRCTN )
NL60405.100.17 ( Other Identifier: Dutch Competent Authority )
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Available on request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: End of the study
Access Criteria: Available on request

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Koen Rovers, Catharina Ziekenhuis Eindhoven:
Colorectal Neoplasms
Peritoneal Neoplasms
Intraperitoneal Injections
Laparoscopy
Aerosols
Chemotherapy, Cancer, Regional Perfusion
Antineoplastic Agents
Leucovorin
Fluorouracil
Platinum
Intraoperative Complications
Postoperative Complications
Drug-Related Side Effects and Adverse Reactions
Disease-free survival
Survival
Mortality
Quality of Life
Costs and Cost Analysis
Translational Medical Research
Clinical Trials, Phase II as topic
PIPAC
Pressurized Intraperitoneal Aerosol Chemotherapy
Pressurised Intraperitoneal Aerosol Chemotherapy
Peritoneum
Cecal Neoplasms
Oxaliplatin
Additional relevant MeSH terms:
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Colorectal Neoplasms
Carcinoma
Peritoneal Neoplasms
Appendiceal Neoplasms
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Abdominal Neoplasms
Peritoneal Diseases
Cecal Neoplasms
Cecal Diseases
Oxaliplatin
Antineoplastic Agents