TY - JOUR
T1 - Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin
T2 - Protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial
AU - De Boer, Nadine Leonie
AU - Brandt-Kerkhof, Alexandra R.M.
AU - Madsen, Eva V.E.
AU - DIepeveen, Marjolein
AU - Van Meerten, Esther
AU - Van Eerden, Ruben A.G.
AU - De Man, Femke M.
AU - Bouamar, Rachida
AU - Koolen, Stijn L.W.
AU - De Hingh, Ignace H.J.T.
AU - Bakkers, Checca
AU - Rovers, Koen P.
AU - Creemers, Geert Jan M.
AU - Deenen, Maarten J.
AU - Kranenburg, Onno W.
AU - Constantinides, Alexander
AU - Mathijssen, Ron H.J.
AU - Verhoef, Cornelis
AU - Burger, Jacobus W.A.
N1 - Funding:
This study is funded by Stichting Coolsingel, grant number 565. The
funding body did not have a role in the design of the study, in the collection,
analysis, and interpretation of data, and in writing the manuscript.
Publisher Copyright:
© Author(s) (or their employer(s)) 2019.
PY - 2019/12/8
Y1 - 2019/12/8
N2 - Introduction Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan. Methods and analysis This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult patients with extensive peritoneal metastases of colorectal origin who have a good performance status and no extra-Abdominal metastases. According to standard work-up for CRS-HIPEC, patients will undergo a diagnostic laparoscopy to score the PCI. In case of a PCI >20, a peritoneal access port will be placed in the abdomen of the patient. Through this port we will administer intraperitoneal irinotecan, in combination with standard systemic treatment consisting of 5-fluorouracil/leucovorin with oxaliplatin and the targeted agent bevacizumab. Therapy consists of a maximum of 12 cycles 2-weekly. Ethics and dissemination This study protocol is approved by a research medical ethics committee (Rotterdam, Netherlands) and the Dutch Competent Authority (CCMO, The Hague, Netherlands). The results of this trial will be submitted for publication in a peer-reviewed scientific journal. Trail registration number NL6988 and NL2018-000479-33; Pre-results.
AB - Introduction Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan. Methods and analysis This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult patients with extensive peritoneal metastases of colorectal origin who have a good performance status and no extra-Abdominal metastases. According to standard work-up for CRS-HIPEC, patients will undergo a diagnostic laparoscopy to score the PCI. In case of a PCI >20, a peritoneal access port will be placed in the abdomen of the patient. Through this port we will administer intraperitoneal irinotecan, in combination with standard systemic treatment consisting of 5-fluorouracil/leucovorin with oxaliplatin and the targeted agent bevacizumab. Therapy consists of a maximum of 12 cycles 2-weekly. Ethics and dissemination This study protocol is approved by a research medical ethics committee (Rotterdam, Netherlands) and the Dutch Competent Authority (CCMO, The Hague, Netherlands). The results of this trial will be submitted for publication in a peer-reviewed scientific journal. Trail registration number NL6988 and NL2018-000479-33; Pre-results.
UR - http://www.scopus.com/inward/record.url?scp=85076375273&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2019-034508
DO - 10.1136/bmjopen-2019-034508
M3 - Article
C2 - 31818845
SN - 2044-6055
VL - 9
JO - BMJ Open
JF - BMJ Open
IS - 12
M1 - e034508
ER -
