PIPAC for Peritoneal Metastases of Colorectal Cancer
- Conditions
- Colorectal NeoplasmsPeritoneal CarcinomatosisAppendiceal NeoplasmsPeritoneal Neoplasms
- Interventions
- Combination Product: repetitive ePIPAC-OX
- Registration Number
- NCT03246321
- Lead Sponsor
- Koen Rovers
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description repetitive ePIPAC-OX repetitive ePIPAC-OX -
- Primary Outcome Measures
Name Time Method Major toxicity 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
Name Time Method Quality of life: QLQ-CR29 Expected (in case of three ePIPAC-OX): 16 weeks QLQ-CR29 at baseline and one and four weeks after each ePIPAC-OX
Cytological tumour response 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 Expected (in case of three ePIPAC-OX): 12 weeks Peritoneal Cancer Index and ascites volume during each ePIPAC-OX
Minor toxicity 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
Major postoperative complications 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
Radiological tumour response 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)
Organ-specific toxicity 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
Hospital stay 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
Biochemical tumour response 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
Pharmacokinetics 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 Expected (in case of three ePIPAC-OX): 12 weeks Number of procedures with intraoperative complications determined during each ePIPAC-OX
Procedure-related characteristics: adhesions Expected (in case of three ePIPAC-OX): 12 weeks Zühlke score determined during each ePIPAC-OX
Minor postoperative complications 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
Readmissions 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
Histopathological tumour response 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
Quality of life: EQ-5D-5L 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 Expected (in case of three ePIPAC-OX): 16 weeks QLQ-C30 at baseline and one and four weeks after each ePIPAC-OX
Progression-free survival 24 months Time between enrolment and clinical, radiological, or macroscopic progression, or death
Costs 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
Procedure-related characteristics: operating time Expected (in case of three ePIPAC-OX): 12 weeks Operating time in minutes determined during each ePIPAC-OX
Overall survival 24 months Time between enrolment and death
Environmental safety of ePIPAC-OX 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
Procedure-related characteristics: blood loss Expected (in case of three ePIPAC-OX): 12 weeks Blood loss in minutes determined during each ePIPAC-OX
Trial Locations
- Locations (2)
Catharina Hospital
🇳🇱Eindhoven, Netherlands
St. Antonius Hospital
🇳🇱Nieuwegein, Netherlands