Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6)

Table 1 Schedule of enrolment, interventions, and assessments of the experimental arm

	Study period
	Enrolment/allocation	Post-allocation							Close-out
	Outpatient clinics	Neoadjuvant treatment	CRS-HIPEC	Adjuvant treatment	3 months after CRS-HIPEC	6 months after CRS-HIPEC	9 months after CRS-HIPEC	Every 6 months	5 years after randomisation
Enrolment/allocation
Eligibility screen	X
Informed consent	X
Allocation	X
Interventions
Chemotherapy		X		X
Bevacizumab		X^a
CRS-HIPEC			X
Thoracoabdominal CT		X^b			X		X	X	X
Questionnaires	X	X^c			X	X	X	X	X
Translational research: blood	X	X^d	X^e	X^d	X		X	X	X
Translational research: tissue			X
Assessments
Baseline characteristics	X
Feasibility of systemic therapy		X	X	X
Safety/toxicity of systemic therapy		X	X	X
Radiological response		X
Histopathological response			X
Surgical characteristics			X
Postoperative morbidity			X		X
Progression-free survival		X	X	X	X	X	X	X	X
Disease-free survival			X	X	X	X	X	X	X
Overall survival		X	X	X	X	X	X	X	X
Health-related quality of life	X	X	X		X	X	X	X	X
Costs	X	X	X		X	X	X	X	X

CRS-HIPEC cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, CT computed tomography^aAdded to the first three (CAPOX) or four (FOLFOX/FOLFIRI) cycles of neoadjuvant chemotherapy
^bAfter three (CAPOX with bevacizumab) or four (FOLFOX/FOLFIRI with bevacizumab) cycles
^cAfter completion of neoadjuvant systemic therapy, before CRS-HIPEC
^dBetween the first and the second cycle of (neo)adjuvant systemic therapy
^e1 day before CRS-HIPEC and 7 days after CRS-HIPEC

ISSN: 1471-2407