Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03246321
Recruitment Status : Recruiting
First Posted : August 11, 2017
Last Update Posted : January 18, 2019
Sponsor:
Information provided by (Responsible Party):
Koen Rovers, Catharina Ziekenhuis Eindhoven

Tracking Information
First Submitted Date  ICMJE August 2, 2017
First Posted Date  ICMJE August 11, 2017
Last Update Posted Date January 18, 2019
Actual Study Start Date  ICMJE October 1, 2017
Estimated Primary Completion Date October 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
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
Original Primary Outcome Measures  ICMJE
 (submitted: August 8, 2017)
Major morbidity [ Time Frame: Expected: 16 weeks ]
Common Terminology Criteria for Adverse Events grade III-V, measured up to 4 weeks after the last PIPAC-procedure
Change History Complete list of historical versions of study NCT03246321 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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
  • Macroscopic tumour response [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Peritoneal Cancer Index and ascites volume during each ePIPAC-OX
  • 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
  • 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
  • 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
  • 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
  • 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
  • Progression-free survival [ Time Frame: 24 months ]
    Time between enrolment and clinical, radiological, or macroscopic progression, or death
  • Overall survival [ Time Frame: 24 months ]
    Time between enrolment and death
  • 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
  • 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.
  • 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
  • Procedure-related characteristics: adhesions [ Time Frame: Expected (in case of three ePIPAC-OX): 12 weeks ]
    Zühlke score determined during each ePIPAC-OX
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2017)
  • Platinum concentrations in the air of the operating room [ Time Frame: Expected: 1 week ]
    Stationary measurements in the operating room and personal measurements at the working places of the personnel (e.g. surgeon, anesthesiologist) and at the position of the patient, measured during the first 3-5 PIPAC-procedures, depending on findings
  • Platinum concentrations on surfaces in the operating room [ Time Frame: Expected: 1 week ]
    Measurements on the surface of equipment and devices (e.g. high pressure injector, filter system) and personal measurements at the working places of the personnel (e.g. clothing, gloves) and at the position of the patient, measured during the first 3-5 PIPAC-procedures, depending on findings
  • Platinum concentrations in plasma of the patient [ Time Frame: Expected: 12 weeks ]
    Total and ultrafiltrated plasma concentrations of platinum, measured at t=0, t=0.5, t=0.75, t=1, t=2, t=4, t=6, and t=8 hours after start of oxaliplatin injection in the first 10 patients, depending on findings
  • Platinum concentrations in excretes (urine, saliva) of the patient [ Time Frame: Expected: 12 week ]
    Measured at t=1, t=3, t=5, and t=7 days after the PIPAC-procedure in the first 10 patients, depending on findings
  • Intraoperative characteristics [ Time Frame: Expected: 12 weeks ]
    Laparoscopic (non-)access, amount of adhesions (Zühlke), ascites volume (ml), blood loss (ml), operating time (minutes), any intraoperative complications (e.g. bleeding, perforation), and any PIPAC-specific technical difficulties, measured during each PIPAC-procedure
  • Minor morbidity [ Time Frame: Expected: 16 weeks ]
    Common Terminology Criteria for Adverse Events grade II, measured up to 4 weeks after the last PIPAC-procedure
  • Hospital stay [ Time Frame: Expected: 16 weeks ]
    Days between PIPAC-procedure and discharge, measured up to 4 weeks after the last PIPAC-procedure
  • Number of readmissions [ Time Frame: Expected: 16 weeks ]
    Hospital readmission after initial discharge, measured up to 4 weeks after the last PIPAC-procedure
  • Number of PIPAC-procedures [ Time Frame: Expected: 52 weeks ]
    Measured in each patient with reasons for discontinuation of further PIPAC-procedures
  • Organ functions [ Time Frame: Expected: 16 weeks ]
    Renal, liver, and haematological function, measured at baseline as well as 12 hours and 4 weeks after each PIPAC-procedure, up to 4 weeks after the last PIPAC-procedure
  • Histopathological tumour response [ Time Frame: Expected: 12 weeks ]
    Assessed with the Peritoneal Regression Scale (PRGS), measured after each second and subsequent PIPAC-procedure
  • Macroscopic intraperitoneal tumour response [ Time Frame: Expected: 12 weeks ]
    Assessed with the Peritoneal Cancer Index (PCI), measured after each second and subsequent PIPAC-procedure
  • Tumour markers [ Time Frame: Expected: 52 weeks ]
    Carcinoembryonic antigen (CEA), measured at baseline as well as 12 hours and 4 weeks after each PIPAC-procedure, and during follow-up every 3 months, up to 52 weeks after inclusion
  • Peritoneal progression free survival [ Time Frame: Expected: 52 weeks ]
    Time between inclusion and macroscopic intraperitoneal disease progression during a second or subsequent PIPAC, or radiological evidence of intraperitoneal disease progression on CT-scan 4 weeks after each PIPAC or during follow-up every 3 months, measured up to 52 weeks after inclusion
  • Systemic progression free survival [ Time Frame: Expected: 52 weeks ]
    Time between inclusion and radiological evidence of systemic disease progression on CT-scan 4 weeks after each PIPAC or during follow-up every 3 months, measured up to 52 weeks after inclusion
  • Disease-specific survival [ Time Frame: Expected: 52 weeks ]
    Months between inclusion and death due to colorectal cancer
  • Overall survival [ Time Frame: Expected: 52 weeks ]
    Months between inclusion and death due to any cause
  • Quality of life [ Time Frame: Expected: 52 weeks ]
    Assessed with EQ5D5L, EORTC-QLQC30, and EORTC-QLQCR29, and measured at baseline, 4 weeks after each PIPAC-procedure, and during follow-up every 3 months, up to 52 weeks after inclusion
  • Costs [ Time Frame: Expected: 52 weeks ]
    Assessed with the iMTA Productivity Cost Questionnaire and iMTA Medical Consumption Questionnaire, and measured every 3 months up to 52 weeks after inclusion
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: August 8, 2017)
  • Collection of tissue and ascites for translational research [ Time Frame: Expected: 12 weeks ]
    During each PIPAC-procedure, ascites or peritoneal fluid is sent for cytology and several peritoneal metastases are biopsied. After processing, these samples are frozen until analysis
  • Collection of blood for translational research [ Time Frame: Expected: 52 weeks ]
    An EDTA tube (10 ml) is drawn at baseline, t=0, t=0.5, t=1, t=2, t=4, t=6, t=8 during/after each PIPAC, 4 weeks after each PIPAC, and during follow-up every 3 months, up to 52 weeks after inclusion. After processing, these samples are frozen until analysis
 
Descriptive Information
Brief Title  ICMJE PIPAC for Peritoneal Metastases of Colorectal Cancer
Official Title  ICMJE 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)
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Neoplasms
  • Peritoneal Neoplasms
  • Appendiceal Neoplasms
  • Peritoneal Carcinomatosis
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: repetitive ePIPAC-OX
Intervention: Combination Product: repetitive ePIPAC-OX
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 8, 2017)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2022
Estimated Primary Completion Date October 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Koen Rovers, MD +31402396351 koen.rovers@catharinaziekenhuis.nl
Contact: Ignace de Hingh, MD, PhD +31402397150 ignace.d.hingh@catharinaziekenhuis.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03246321
Other Study ID Numbers  ICMJE NL60405.100.17
2017-000927-29 ( EudraCT Number )
NTR6603 ( Registry Identifier: NTR )
ISRCTN89947480 ( Registry Identifier: ISRCTN )
NL60405.100.17 ( Other Identifier: Dutch Competent Authority )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Available on request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: End of the study
Access Criteria: Available on request
Responsible Party Koen Rovers, Catharina Ziekenhuis Eindhoven
Study Sponsor  ICMJE Koen Rovers
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Ignace de Hingh, MD, PhD Catharina Hospital, Eindhoven, Netherlands
Principal Investigator: Djamila Boerma, MD, PhD St Antonius Hospital, Nieuwegein, Netherlands
PRS Account Catharina Ziekenhuis Eindhoven
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP