Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone: a multicentre, open-label, parallel-group, phase II-III, randomised superiority study (CAIRO6).

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 298

Inclusion Criteria

Eligible patients are adults who have:
* a World Health Organisation (WHO) performance status of <=1;
* histological or cytological proof of PM of a non-appendiceal colorectal
adenocarcinoma with <=50% of the tumour cells being signet ring cells;
* resectable disease determined by abdominal computed tomography (CT) and a
diagnostic laparoscopy/laparotomy;
* no evidence of systemic colorectal metastases within three months prior to
enrolment;
* no systemic therapy for colorectal cancer within six months prior to
enrolment;
* no contraindications for CRS-HIPEC;
* no previous CRS-HIPEC;
* no concurrent malignancies that interfere with the planned study treatment or
the prognosis of resected colorectal PM.

Exclusion Criteria

Patients are excluded in case of any comorbidity or condition that prevents
safe administration of the planned perioperative systemic therapy, determined
by the treating medical oncologist, e.g.:
* Inadequate bone marrow, renal, or liver functions (e.g. haemoglobin <6.0
mmol/L, neutrophils <1.5 x 109/L, platelets <100 x 109/L, serum creatinine >1.5
x ULN, creatinine clearance <30 ml/min, bilirubin >2 x ULN, serum liver
transaminases >5 x ULN);
* Previous intolerance of fluoropyrimidines or both oxaliplatin and irinotecan;
* Dehydropyrimidine dehydrogenase deficiency;
* Serious active infections;
* Severe diarrhoea;
* Stomatitis or ulceration in the mouth or gastrointestinal tract;
* Recent major cardiovascular events;
* Unstable or uncompensated respiratory or cardiac disease;
* Bleeding diathesis or coagulopathy;
* Pregnancy or lactation.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Endpoints of the phase II study are to explore the feasibility of accrual, the<br /><br>feasibility, safety, and tolerance of perioperative systemic therapy, and the<br /><br>radiological/histological response of colorectal PM to neoadjuvant systemic<br /><br>therapy. The primary endpoint of the phase III study is 3-year overall<br /><br>survival, which is hypothesised to be 50% in the control arm and 65% in the<br /><br>experimental arm, thereby requiring 358 patients (179 in each arm). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are surgical characteristics, grade >=3 postoperative<br /><br>morbidity, progression-free survival, disease-free survival, health-related<br /><br>quality of life, costs, major systemic therapy related toxicity, and objective<br /><br>radiological and histological response rates of colorectal PM to neoadjuvant<br /><br>systemic therapy.</p><br>