Intraperitoneal irinotecan with concomitant FOLFOX and bevacizumab for patients with unresectable colorectal peritoneal metastases: protocol of the multicentre, open-label, phase II, INTERACT-II trial.

Autor:	van de Vlasakker VCJ; Department of Surgery, Catharina Ziekenhuis, Eindhoven, The Netherlands., Guchelaar NAD; Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands., van den Heuvel TBM; Department of Surgery, Catharina Ziekenhuis, Eindhoven, The Netherlands., Lurvink RJ; Department of Surgery, Catharina Ziekenhuis, Eindhoven, The Netherlands., van Meerten E; Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands., Bax RJF; Department of Medical Oncology, Catharina Hospital, Eindhoven, The Netherlands., Creemers GM; Department of Medical Oncology, Catharina Hospital, Eindhoven, The Netherlands., van Hellemond IEG; Department of Medical Oncology, Catharina Hospital, Eindhoven, The Netherlands., Brandt-Kerkhof ARM; Department of Surgical Oncology, Erasmus MC, Rotterdam, The Netherlands., Madsen EVE; Department of Surgical Oncology, Erasmus MC, Rotterdam, The Netherlands., Nederend J; Department of Radiology, Catharina Hospital, Eindhoven, The Netherlands., Koolen SLW; Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands.; Department of Pharmacy, Erasmus MC, Rotterdam, The Netherlands., Nienhuijs SW; Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands., Kranenburg O; Department of Surgical Oncology and Utrecht Platform for Organoid Technology, UMC Utrecht, Utrecht, The Netherlands., de Hingh IHJT; Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.; Maastricht University GROW School for Oncology and Reproduction, Maastricht, The Netherlands., Verhoef C; Department of Surgical Oncology, Erasmus MC, Rotterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC, Rotterdam, The Netherlands., Burger JWA; Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands pim.burger@catharinaziekenhuis.nl.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2024 Jan 18; Vol. 14 (1), pp. e077667. Date of Electronic Publication: 2024 Jan 18.
DOI:	10.1136/bmjopen-2023-077667
Abstrakt:	Introduction: The peritoneum is the second most affected organ for the dissemination of colorectal cancer (CRC). Patients with colorectal peritoneal metastases (CPM) face a poor prognosis, despite the majority of patients being treated with palliative systemic therapy. The efficacy of palliative systemic therapy is limited due to the plasma-peritoneum barrier. The poor prognosis of unresectable CPM patients has resulted in the development of new treatment strategies where systemic therapy is combined with local, intraperitoneal chemotherapy. In the recently published phase I study, the maximum tolerated dose and thus the recommended phase II dose of intraperitoneal irinotecan was investigated and determined to be 75 mg. In the present study, the overall survival after treatment with 75 mg irinotecan with concomitant mFOLFOX4 and bevacizumab will be investigated. Materials and Methods: In this single-arm phase II study in two Dutch tertiary referral centres, 85 patients are enrolled. Eligibility criteria are an adequate performance status and organ function, histologically confirmed microsatellite stable and unresectable CPM, no previous palliative therapy for CRC, no systemic therapy<6 months for CRC prior to enrolment and no previous cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). Patients will undergo a diagnostic laparoscopy as standard work-up for CPM and if the peritoneal disease is considered unresectable (eg, Peritoneal Cancer Index (PCI)>20, too extensive small bowel involvement), a peritoneal access port and a port-a-cath are placed for administration of intraperitoneal and intravenous chemotherapy, respectively. Patients may undergo up to 12 cycles of study treatment. Each cycle consists of intravenous mFOLFOX4 with bevacizumab and concomitant intraperitoneal irinotecan (75 mg), which is repeated every 2 weeks, with a maximum of 12 cycles. Modified FOLFOX-4 regimen consists of 85 mg/m 2 oxaliplatin plus 200 mg/m 2 LV and 5-FU 400 mg/m 2 bolus on day 1 followed by 1600 mg/m 2 5-FU as a 46 hours infusion. Study treatment ends after the 12th cycle, or earlier in case of disease progression or unacceptable toxicity. The primary outcome is overall survival and key secondary outcomes are progression-free survival, safety (measured by the amount of grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0)), patient-reported outcomes and pharmacokinetics of irinotecan. It is hypothesised that the trial treatment will lead to a 4 month increase in overall survival; from a median of 12.2 to 16.2 months. Ethics and Dissemination: This study is approved by the Dutch Authority (CCMO, the Hague, the Netherlands), by a central medical ethics committee (MEC-U, Nieuwegein, the Netherlands) and by the institutional research boards of both research centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals. Trial Registration Number: NCT06003998. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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