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

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.

Primary Outcomes

Secondary Outcomes

• Quality of life: QLQ-CR29(Expected (in case of three ePIPAC-OX): 16 weeks)
• Cytological tumour response(Expected (in case of three ePIPAC-OX): 12 weeks)
• Macroscopic tumour response(Expected (in case of three ePIPAC-OX): 12 weeks)
• Minor toxicity(Expected (in case of three ePIPAC-OX): 16 weeks)
• Major postoperative complications(Expected (in case of three ePIPAC-OX): 16 weeks)
• Radiological tumour response(Expected (in case of three ePIPAC-OX): 16 weeks)
• Organ-specific toxicity(Expected (in case of three ePIPAC-OX): 16 weeks)
• Hospital stay(Expected (in case of three ePIPAC-OX): 16 weeks)
• Biochemical tumour response(Expected (in case of three ePIPAC-OX): 16 weeks)
• Pharmacokinetics(Expected (in case of three ePIPAC-OX): 13 weeks)
• Procedure-related characteristics: intraoperative complications(Expected (in case of three ePIPAC-OX): 12 weeks)
• Procedure-related characteristics: adhesions(Expected (in case of three ePIPAC-OX): 12 weeks)
• Minor postoperative complications(Expected (in case of three ePIPAC-OX): 16 weeks)
• Readmissions(Expected (in case of three ePIPAC-OX): 16 weeks)
• Histopathological tumour response(Expected (in case of three ePIPAC-OX): 12 weeks)
• Quality of life: EQ-5D-5L(Expected (in case of three ePIPAC-OX): 16 weeks)
• Quality of life: QLQ-C30(Expected (in case of three ePIPAC-OX): 16 weeks)
• Progression-free survival(24 months)
• Costs(Expected (in case of three ePIPAC-OX): 16 weeks)
• Procedure-related characteristics: operating time(Expected (in case of three ePIPAC-OX): 12 weeks)
• Overall survival(24 months)
• Environmental safety of ePIPAC-OX(1 week (measured only during the first three procedures in the study))
• Procedure-related characteristics: blood loss(Expected (in case of three ePIPAC-OX): 12 weeks)