TY - JOUR
T1 - First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II)
AU - Lurvink, R.J.
AU - Rauwerdink, P.
AU - Rovers, K.P.
AU - Wassenaar, E.C.E.
AU - Deenen, M.J.
AU - Nederend, J.
AU - Huysentruyt, C.J.R.
AU - van 't Erve, I.
AU - Fijneman, R.J.A.
AU - van der Hoeven, E.J.R.J.
AU - Seldenrijk, C.A.
AU - Constantinides, A.
AU - Kranenburg, O.
AU - Los, M.
AU - Herbschleb, K.H.
AU - Thijs, A.M.J.
AU - Creemers, G.J.M.
AU - Burger, J.W.A.
AU - Wiezer, M.J.
AU - Nienhuijs, S.W.
AU - Boerma, D.
AU - de Hingh, I.H.J.T.
PY - 2021
Y1 - 2021
N2 - Introduction Despite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM. Methods and analysis In this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Key eligibility criteria are a good performance status, pathologically proven isolated unresectable CPM, no previous palliative systemic therapy for colorectal cancer, no (neo)adjuvant systemic therapy <= 6 months prior to enrolment and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC). Patients receive three cycles of bidirectional therapy. Each cycle consists of 6 weeks first-line palliative systemic therapy at the medical oncologists' decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg/m(2)) with an intraoperative bolus of intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m(2)). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with-and procedures leading to-grade >= 3 adverse events (Common Terminology Criteria for Adverse Events V.5.0) up to 4 weeks after the last procedure. Key secondary outcomes include the number of bidirectional cycles in each patient, treatment-related characteristics, grade <= 2 adverse events, tumour response (histopathological, cytological, radiological, biochemical, macroscopic and ascites), patient-reported outcomes, systemic pharmacokinetics of oxaliplatin, costs, progression-free survival and overall survival. Ethics and dissemination This study is approved by the Dutch competent authority, a medical ethics committee and the institutional review boards of both study centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals.
AB - Introduction Despite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM. Methods and analysis In this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Key eligibility criteria are a good performance status, pathologically proven isolated unresectable CPM, no previous palliative systemic therapy for colorectal cancer, no (neo)adjuvant systemic therapy <= 6 months prior to enrolment and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC). Patients receive three cycles of bidirectional therapy. Each cycle consists of 6 weeks first-line palliative systemic therapy at the medical oncologists' decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg/m(2)) with an intraoperative bolus of intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m(2)). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with-and procedures leading to-grade >= 3 adverse events (Common Terminology Criteria for Adverse Events V.5.0) up to 4 weeks after the last procedure. Key secondary outcomes include the number of bidirectional cycles in each patient, treatment-related characteristics, grade <= 2 adverse events, tumour response (histopathological, cytological, radiological, biochemical, macroscopic and ascites), patient-reported outcomes, systemic pharmacokinetics of oxaliplatin, costs, progression-free survival and overall survival. Ethics and dissemination This study is approved by the Dutch competent authority, a medical ethics committee and the institutional review boards of both study centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals.
KW - chemotherapy
KW - colorectal surgery
KW - gastrointestinal tumours
KW - INSTRUMENT
KW - TRIALS
KW - PRECIPITATION
KW - RATIONALE
KW - CARCINOMATOSIS
KW - PROPOSAL
KW - QUESTIONNAIRE
KW - CANCER
U2 - 10.1136/bmjopen-2020-044811
DO - 10.1136/bmjopen-2020-044811
M3 - Article
C2 - 33785492
SN - 2044-6055
VL - 11
JO - BMJ Open
JF - BMJ Open
IS - 3
M1 - e044811
ER -