Colorectal cancer with isolated peritoneal metastases
Conditions
Interventions
At the discretion of the treating medical oncologist, perioperative systemic therapy consists of either:
• Four three-weekly neoadjuvant and adjuvant cycles of CAPOX (130 mg/m2body-surface area [BSA
1000 mg/m2BSA of capecitabine, orally twice daily on days 1-14), with bevacizumab (7.5 mg/kg body weight, IV on day 1) added to the first three neoadjuvant cycles, or
• Six two-weekly neoadjuvant and adjuvant cycles of FOLFOX (85 mg/m2BSA of oxaliplatin, IV on day 1
400 mg/m2BSA of leucovorin, IV on day 1
400/2400 mg/m2BSA of bolus/continuous 5-fluorouracil, IV on day 1-2), with bevacizumab (5 mg/kg body weight, IV on day 1) added to the first four neoadjuvant cycles, or
• Six two-weekly neoadjuvant cycles of FOLFIRI (180 mg/m2BSA of irinotecan, IV on day 1
400/2400 mg/m2BSA of bolus/continuous 5-fluorouracil, IV on day 1-2) and either four three-weekly (1000 mg/m2BSA of capecitabine, orally twice daily on days 1-14) or six two-weekly (400 mg/m2BSA of le
400/2400 mg/m2BSA of bolus/continuous 5-fluorouracil, IV on day 1-2) adjuvant cycles of fluoropyrimidine monotherapy, with bevacizumab (5 mg/kg body weight, IV on day 1) added to the first four neoadj
Sponsors
Catharina Hospital
Michelangelolaan 2
5623 EJ, Eindhoven
The Netherlands
Eligibility
Inclusion criteria
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. Importantly, enrolment is allowed for patients with radiologically non-measurable disease. The diagnostic laparoscopy/laparotomy may be performed in a referring centre, provided that the peritoneal cancer index (PCI) is appropriately scored and documented before enrolment.
Exclusion criteria
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 1.5 x ULN, creatinine clearance 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcomes of the phase II study are to explore: •the feasibility of accrual, based on the total accrual rate, the accrual rate in each study centre, and screening failures (time point: not applicable); •the feasibility of perioperative systemic therapy, based on the number of patients that (1) start/complete neoadjuvant systemic therapy with/without dose reductions, (2) are scheduled for CRS-HIPEC, (3) undergo complete CRS-HIPEC, and (4) start/complete adjuvant systemic therapy with/without dose reductions (time point: six to nine months after randomisation); •the safety of perioperative systemic therapy, based on the number of patients with (1) systemic therapy related toxicity, defined as grade ≥2 according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0, up to one month after the last administration of systemic therapy, and (2) postoperative morbidity, defined as grade ≥2 according to Clavien-Dindo, up to three months after CRS-HIPEC (time point: six to nine months after randomisation); • the tolerance of perioperative systemic therapy, based on health-related quality of life extracted from EQ-5D-5L, QLQ-C30, and QLQ-CR29 during study treatment (time point: six to nine months after randomisation); • the radiological and histological response of colorectal PM to neoadjuvant systemic therapy, based on central review of thoracoabdominal CT and resected specimens during CRS-HIPEC, respectively (time point: three to four months after randomisation). The primary outcome is 3-year overall survival, defined as the number of patients who are alive three years after randomisation (time point: three years after randomisation). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcomes of the phase III study in both arms are: • progression-free survival, defined as the time between randomisation and disease progression before CRS-HIPEC, CRS-HIPEC in case of unresectable disease, radiological proof of recurrence, or death (time point: three years after randomisation); • disease-free survival, defined as the time between CRS-HIPEC and radiological proof of recurrence or death (time point: three years after randomisation); • health-related quality of life, extracted from questionnaires (EQ-5D-5L, QLQ-C30, QLQ-CR29) before study treatment, after neoadjuvant systemic therapy (experimental arm), every three months after CRS-HIPEC until one year postoperatively, and every six months thereafter until five years after randomisation (time point: three years after randomisation); • costs, extracted from questionnaires (iMTA productivity cost questionnaire, iMTA medical consumption questionnaire) before study treatment, after neoadjuvant systemic therapy (experimental arm), every three months after CRS-HIPEC until one year postoperatively, and every six months thereafter until five years after randomisation (time point: three years after randomisation); • surgical characteristics, e.g. PCI, intraoperative complications, operating time, resections, completeness of cytoreduction, hospital stay (time point: three to four months after randomisation); • the number of patients with major postoperative morbidity, defined as grade ≥3 according to Clavien-Dindo, up to three months after CRS-HIPEC (time point: six to nine months after randomisation). Secondary outcomes in the experimental arm are: • The number of patients with major systemic therapy related toxicity, defined as grade ≥3 according to the CTCAE, up to one month after the last administration of systemic therapy; • The number of patients with an objective radiological and histological response of colorectal PM to neoadjuvant systemic therapy, determined by ce | — |
Contacts
Public ContactKoen Rovers
PO Box 1350
Outcome results
None listed