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Perioperative Systemic Therapy for Isolated Resectable Colorectal Peritoneal Metastases (CAIRO6)

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ClinicalTrials.gov Identifier: NCT02758951
Recruitment Status : Recruiting
First Posted : May 3, 2016
Last Update Posted : January 29, 2019
Sponsor:
Collaborators:
Dutch Cancer Society
Comprehensive Cancer Centre The Netherlands
Hoffmann-La Roche
Information provided by (Responsible Party):
Koen Rovers, Catharina Ziekenhuis Eindhoven

Tracking Information
First Submitted Date  ICMJE April 26, 2016
First Posted Date  ICMJE May 3, 2016
Last Update Posted Date January 29, 2019
Actual Study Start Date  ICMJE June 1, 2017
Estimated Primary Completion Date August 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2019)
  • Phase II (n=80): feasibility of perioperative systemic therapy (1) [ Time Frame: Approximately one month after randomisation ]
    Number of patients that start neoadjuvant systemic therapy
  • Phase II (n=80): feasibility of perioperative systemic therapy (2) [ Time Frame: Approximately four months after randomisation ]
    Number of patients that complete neoadjuvant systemic therapy
  • Phase II (n=80): feasibility of perioperative systemic therapy (3) [ Time Frame: Approximately four months after randomisation ]
    Number of patients with a dose reduction during neoadjuvant systemic therapy
  • Phase II (n=80): feasibility of perioperative systemic therapy (4) [ Time Frame: Approximately five months after randomisation ]
    Number of patients that are scheduled for CRS-HIPEC
  • Phase II (n=80): feasibility of perioperative systemic therapy (5) [ Time Frame: Approximately five months after randomisation ]
    Number of patients that undergo complete CRS-HIPEC
  • Phase II (n=80): feasibility of perioperative systemic therapy (6) [ Time Frame: Approximately eight months after randomisation ]
    Number of patients that start adjuvant systemic therapy
  • Phase II (n=80): feasibility of perioperative systemic therapy (7) [ Time Frame: Approximately eleven months after randomisation ]
    Number of patients that complete adjuvant systemic therapy
  • Phase II (n=80): feasibility of perioperative systemic therapy (8) [ Time Frame: Approximately eleven months after randomisation ]
    Number of patients with a dose reduction during adjuvant systemic therapy
  • Phase II (n=80): safety of perioperative systemic therapy (1) [ Time Frame: Up to one month after the last administration of systemic therapy (approximately one year after randomisation) ]
    Number of patients with systemic related toxicity, defined as grade 2 or higher according to CTCAE v4.0
  • Phase II (n=80): safety of perioperative systemic therapy (2) [ Time Frame: Up to three months after CRS-HIPEC (approximately eight months after randomisation) ]
    Number of patients with postoperative morbidity, defined as grade 2 or higher according to Clavien-Dindo
  • Phase II (n=80): tolerance of perioperative systemic therapy (1) [ Time Frame: Up to six months after CRS-HIPEC (approximately eleven months after randomisation) ]
    EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) during the initial treatment
  • Phase II (n=80): tolerance of perioperative systemic therapy (2) [ Time Frame: Up to six months after CRS-HIPEC (approximately eleven months after randomisation) ]
    European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire C30 during the initial treatment
  • Phase II (n=80): tolerance of perioperative systemic therapy (3) [ Time Frame: Up to six months after CRS-HIPEC (approximately eleven months after randomisation) ]
    European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire CR29 during the initial treatment
  • Phase II (n=80): radiological response of colorectal PM to neoadjuvant systemic therapy [ Time Frame: Approximately three months after randomisation ]
    Number of patients with an objective radiological response. Central review of thoracoabdominal CT during neoadjuvant systemic therapy. Classification not defined a priori.
  • Phase II (n=80): histological response of colorectal PM to neoadjuvant systemic therapy [ Time Frame: Approximately five months after randomisation ]
    Number of patients with an objective histological response. Central review of specimens resected during CRS-HIPEC. Classification not defined a priori.
  • Phase III (n=358): overall survival [ Time Frame: Up to five years after randomisation ]
    Time between randomisation and death
  • Phase III (n=358): progression-free survival [ Time Frame: Up to five years after randomisation ]
    Time between randomisation and disease progression before CRS-HIPEC, CRS-HIPEC in case of unresectable disease, radiological proof of recurrence, or death
  • Phase III (n=358): disease-free survival [ Time Frame: Up to five years after randomisation ]
    Time between CRS-HIPEC and radiological proof of recurrence or death in operated patients
  • Phase III (n=358): health-related quality of life (1) [ Time Frame: Up to five years after randomisation ]
    EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)
  • Phase III (n=358): health-related quality of life (2) [ Time Frame: Up to five years after randomisation ]
    European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire C30
  • Phase III (n=358): health-related quality of life (3) [ Time Frame: Up to five years after randomisation ]
    European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire CR29
  • Phase III (n=358): costs (1) [ Time Frame: Up to five years after randomisation ]
    Institute for Medical Technology Assessment Productivity Cost Questionnaire
  • Phase III (n=358): costs (2) [ Time Frame: Up to five years after randomisation ]
    Institute for Medical Technology Assessment Medical Consumption Questionnaire
  • Phase III (n=358): major postoperative morbidity [ Time Frame: Up to three months after CRS-HIPEC (approximately eight months after randomisation) ]
    Number of patients with postoperative morbidity, defined as grade 2 or higher according to Clavien-Dindo
  • Phase III (n=358): major systemic therapy related toxicity [ Time Frame: Up to one month after the last administration of systemic therapy (approximately one year after randomisation) ]
    Number of patients with systemic related toxicity, defined as grade 2 or higher according to CTCAE v4.0
  • Phase III (n=358): radiological response of colorectal PM to neoadjuvant systemic therapy [ Time Frame: Approximately three months after randomisation ]
    Number of patients with an objective radiological response. Central review of thoracoabdominal CT during neoadjuvant systemic therapy. Classification determined after exploration of the radiological response in the phase II study
  • Phase III (n=358): histological response of colorectal PM to neoadjuvant systemic therapy [ Time Frame: Approximately five months after randomisation ]
    Number of patients with an objective histological response. Central review of specimens resected during CRS-HIPEC. Classification determined after exploration of the histological response in the phase II study.
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2016)
  • Major morbidity (Clavien-Dindo grade III-V). [ Time Frame: 90 days after cytoreductive surgery and HIPEC. ]
    Primary endpoint of the phase II study (n=80).
  • Overall survival. [ Time Frame: 3 years after diagnosis with peritoneal metastases of colorectal cancer (PMCRC). ]
    Determined during regular oncological follow-up at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after cytoreductive surgery and HIPEC.
Change History Complete list of historical versions of study NCT02758951 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2016)
  • Number of patients included 1 year after start of recruitment of the last participating centre. [ Time Frame: 1 year after start of recruitment at the last participating centre. ]
    Secondary endpoint of the phase II study (n=80). Randomisation is deemed feasible if >80 patients are recruited during the first year after start of recruitment at all participating centres.
  • Overall survival. [ Time Frame: 5 years after diagnosis with peritoneal metastases of colorectal cancer. ]
    Determined during regular oncological follow-up at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after cytoreductive surgery and HIPEC.
  • Disease free survival. [ Time Frame: 3 years and 5 years after cytoreductive surgery and HIPEC. ]
    Determined during regular oncological follow-up at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after cytoreductive surgery and HIPEC.
  • Procedure related characteristics of cytoreductive surgery and HIPEC (i.e. blood loss, operative time). [ Time Frame: During cytoreductive surgery and HIPEC, which is about 3 weeks after randomisation in the control arm, and about 4 months after randomisation in the experimental arm. ]
    Surgeon documents operative time, blood loss, number of resections performed, etcetera.
  • Peritoneal Cancer Index (PCI) Score. [ Time Frame: During cytoreductive surgery and HIPEC, which is about 3 weeks after randomisation in the control arm, and about 4 months after randomisation in the experimental arm. ]
    Surgeon registers the PCI score directly after laparotomy.
  • Completeness of Cytoreduction (CC) Score. [ Time Frame: During cytoreductive surgery and HIPEC, which is about 3 weeks after randomisation in the control arm, and about 4 months after randomisation in the experimental arm. ]
    Surgeon registers the CC score directly after cytoreductive surgery.
  • Severe postoperative complications (Clavien-Dindo grade III-V). [ Time Frame: in-hospital, and 30 and 90 days after cytoreductive surgery and HIPEC. ]
  • Postoperative complications (Clavien-Dindo grade I-II). [ Time Frame: in-hospital, and 30 and 90 days after cytoreductive surgery and HIPEC. ]
  • Hospital stay. [ Time Frame: At the day of discharge from the general surgical ward, which is usually 1-2 weeks after cytoreductive surgery and HIPEC. ]
    Surgeon documents day of discharge from the general surgical ward.
  • ICU stay. [ Time Frame: At the day of discharge from ICU to the ward, which is usually 1-2 days after cytoreductive surgery and HIPEC. ]
    Surgeon documents day of discharge from ICU.
  • Quality of life. [ Time Frame: 6 months, 1 year, 3 year, and 5 year after cytoreductive surgery and HIPEC. ]
    EQ5D questionnaire, EORTC QLQ C30 questionnaire, EORTC QLQ CR29 questionnaire.
  • Cost-effectiveness. [ Time Frame: At 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, and 60 months after cytoreductive surgery and HIPEC. ]
    iMTA Productivity Cost Questionnaire & iMTA Medical Consumption Questionnaire
  • % of patients able to complete their full neoadjuvant regimen, and reason(s) for not completing and/or dose reduction (experimental arm). [ Time Frame: During the full course of neoadjuvant systemic therapy, up to 3-4 months after randomisation ]
  • % of patients able to complete their full adjuvant regimen, and reason(s) for not complete and/or dose reduction (experimental arm). [ Time Frame: During the full course of adjuvant systemic therapy, up to 4-5 months after cytoreductive surgery and HIPEC. ]
  • Treatment related toxicity of neoadjuvant systemic therapy (experimental arm). [ Time Frame: During the full course of neoadjuvant systemic therapy, up to 3-4 months after randomisation ]
    NCICTCAE v4.0
  • Treatment related toxicity of adjuvant systemic therapy (experimental arm). [ Time Frame: During the full course of adjuvant systemic therapy, up to 4-5 months after cytoreductive surgery and HIPEC. ]
    NCICTCAE v4.0
  • % of patients eligible for cytoreductive surgery and HIPEC after neoadjuvant systemic therapy (experimental arm). [ Time Frame: After the full course of neoadjuvant systemic therapy, which is usually +/- 4 months after randomisation. ]
  • Overall survival in patients with disease progression while on neoadjuvant systemic therapy (experimental arm). [ Time Frame: 1 year, 3 year, 5 year ]
    Determined during regular oncological follow-up at 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after cytoreductive surgery and HIPEC was initially planned.
  • Morphological tumour response to neoadjuvant systemic therapy, as assessed by the RECIST criteria. [ Time Frame: During restaging with CT-scan, which is usually +/- 3 months after randomisation ]
  • Pathological tumour response to neoadjuvant systemic therapy, as assessed by the Mandard tumour regression grade. [ Time Frame: 1-2 weeks after cytoreductive surgery and HIPEC ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Perioperative Systemic Therapy for Isolated Resectable Colorectal Peritoneal Metastases
Official Title  ICMJE Perioperative Systemic Therapy and Cytoreductive Surgery With HIPEC Versus Upfront Cytoreductive Surgery With HIPEC Alone for Isolated Resectable Colorectal Peritoneal Metastases: a Multicentre, Open-label, Parallel-group, Phase II-III, Randomised Superiority Study
Brief Summary This is a multicentre, open-label, parallel-group, phase II-III, superiority study that randomises patients with isolated resectable colorectal peritoneal metastases in a 1:1 ratio to receive either perioperative systemic therapy and cytoreductive surgery with HIPEC (experimental arm) or upfront cytoreductive surgery with HIPEC alone (control arm).
Detailed Description

Rationale: cytoreductive surgery with HIPEC (CRS-HIPEC) is a curative intent treatment for patients with isolated resectable colorectal peritoneal metastases (PM). Upfront CRS-HIPEC alone is the standard treatment in the Netherlands. The addition of neoadjuvant and adjuvant systemic therapy, together commonly referred to as perioperative systemic therapy, to CRS-HIPEC could have benefits and drawbacks. Potential benefits are eradication of systemic micrometastases, preoperative intraperitoneal tumour downstaging, elimination of post-surgical residual cancer cells, and improved patient selection for CRS-HIPEC. Potential drawbacks are preoperative disease progression and secondary unresectability, systemic therapy related toxicity, increased postoperative morbidity, decreased quality of life, and higher costs. Currently, there is a complete lack of randomised studies that prospectively compare the oncological efficacy of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone. Notwithstanding this lack of evidence, perioperative systemic therapy is widely administered to patients with isolated resectable colorectal PM. However, administration and timing of perioperative systemic therapy vary substantially between countries, hospitals, and guidelines. More importantly, it remains unknown whether perioperative systemic therapy has an intention-to-treat benefit in this setting. Therefore, this study randomises patients with isolated resectable colorectal PM to receive either perioperative systemic therapy (experimental arm) or upfront CRS-HIPEC alone (control arm).

Study design: multicentre, open-label, parallel-group, phase II-III, randomised superiority study.

Setting: nine Dutch tertiary referral centres qualified for the surgical treatment of colorectal PM.

Objectives: objectives of the phase II study (80 patients) are to explore the feasibility of accrual, the feasibility, safety, and tolerance of perioperative systemic therapy, and the radiological and histological response of colorectal PM to neoadjuvant systemic therapy. The primary objective of the phase III study (an additional 278 patients) is to compare survival outcomes between both arms. Secondary objectives are to compare surgical characteristics, major postoperative morbidity, health-related quality of life, and costs between both arms. Other objectives are to assess major systemic therapy related toxicity and the objective radiological and histological response of colorectal PM to neoadjuvant systemic therapy.

Study population: adults who have a good performance status, histological or cytological proof of PM of a colorectal adenocarcinoma, resectable disease, no systemic colorectal metastases within three months prior to enrolment, no systemic therapy for colorectal cancer within six months prior to enrolment, no previous CRS-HIPEC, no contraindications for the planned systemic treatment or CRS-HIPEC, and no relevant concurrent malignancies.

Randomisation and stratification: eligible patients are randomised in a 1:1 ratio by using central randomisation software with stratified minimisation by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous onset of PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C.

Intervention: at the discretion of the treating medical oncologist, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by either four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles.

Outcomes: outcomes of the phase II study are to explore the feasibility of accrual, the feasibility, safety, and tolerance of perioperative systemic therapy, and the radiological/histological response of colorectal PM to neoadjuvant systemic therapy. The primary outcome of the phase III study is 3-year overall survival, which is hypothesised to be 50% in the control arm and 65% in the experimental arm, thereby requiring 358 patients (179 in each arm). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histological response rates of colorectal PM to neoadjuvant systemic therapy.

Burden, risks, and benefits associated with participation: it is hypothesised that perioperative systemic therapy and CRS-HIPEC (experimental arm) significantly improve the overall survival of patients with isolated resectable colorectal PM compared to the current standard treatment in the Netherlands: upfront CRS-HIPEC alone (control arm). This potential overall survival benefit should be weighed against the burden and risks of the experimental arm. The most important are: additional hospital visits for the perioperative systemic therapy, preoperative disease progression and secondary unresectability, increased postoperative morbidity, systemic therapy related toxicity, and an intensified and prolonged initial treatment that could decrease health-related quality of life. The investigators feel that the potential overall survival benefit of the experimental arm outweighs the burden and risks (that are closely monitored in the phase II study).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Neoplasm
  • Colorectal Cancer
  • Colorectal Neoplasms Malignant
  • Colorectal Carcinoma
  • Colorectal Adenocarcinoma
  • Peritoneal Neoplasms
  • Peritoneal Carcinomatosis
  • Peritoneal Cancer
  • Peritoneal Metastases
  • Peritoneal Neoplasm Malignant Secondary Carcinomatosis
  • Peritoneal Neoplasm Malignant Secondary
Intervention  ICMJE
  • Other: Perioperative systemic therapy
    Neoadjuvant systemic therapy should start within four weeks after randomisation. Adjuvant systemic therapy should start within twelve weeks after CRS-HIPEC. In case of unacceptable toxicity or contraindications to oxaliplatin or irinotecan in the neoadjuvant setting, CAPOX or FOLFOX may be switched to FOLFIRI and vice versa. In case of unacceptable toxicity or contraindications to oxaliplatin in the adjuvant setting, CAPOX of FOLFOX may be switched to fluoropyrimidine monotherapy. Dose reduction, prohibited concomitant care, permitted concomitant care, and strategies to improve adherence are not specified a priori, but left to the discretion of the treating medical oncologist. Perioperative systemic therapy can be prematurely discontinued due to radiological or clinical disease progression, unacceptable toxicity, physicians decision, or at patients request.
  • Combination Product: Perioperative CAPOX-bevacizumab
    Four three-weekly neoadjuvant and adjuvant cycles of CAPOX (130 mg/m2 body-surface area [BSA] of oxaliplatin, intravenously [IV] on day 1; 1000 mg/m2 BSA 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.
  • Combination Product: Perioperative FOLFOX-bevacizumab
    Six two-weekly neoadjuvant and adjuvant cycles of FOLFOX (85 mg/m2 body-surface area [BSA] of oxaliplatin, intravenously [IV] on day 1; 400 mg/m2 BSA of leucovorin, IV on day 1; 400/2400 mg/m2 BSA 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.
  • Combination Product: Perioperative FOLFIRI-bevacizumab
    Six two-weekly neoadjuvant cycles of FOLFIRI (180 mg/m2 body-surface area [BSA] of irinotecan, intravenously [IV] on day 1; 400 mg/m2 BSA of leucovorin, IV on day 1; 400/2400 mg/m2 BSA of bolus/continuous 5-fluorouracil, IV on day 1-2) and either four three-weekly (capecitabine (1000 mg/m2 BSA, orally twice daily on days 1-14) or six two-weekly (400 mg/m2 BSA of leucovorin, IV on day 1; 400/2400 mg/m2 BSA 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 neoadjuvant cycles.
  • Procedure: CRS-HIPEC, experimental arm
    CRS-HIPEC is performed according to the Dutch protocol in all study centres. The choice of HIPEC medication (oxaliplatin or mitomycin C) is left to the discretion of the treating physician, since neither one has a favourable safety or efficacy. CRS-HIPEC should be performed within six weeks after completion of neoadjuvant systemic therapy, and at least six weeks after the last administration of bevacizumab in order to minimise the risk of bevacizumab-related postoperative complications.
  • Procedure: CRS-HIPEC, control arm
    CRS-HIPEC is performed according to the Dutch protocol in all study centres. The choice of HIPEC medication (oxaliplatin or mitomycin C) is left to the discretion of the treating physician, since neither one has a favourable safety or efficacy. CRS-HIPEC should be performed within six weeks after randomisation.
Study Arms  ICMJE
  • Experimental: Perioperative systemic therapy and CRS-HIPEC

    At the discretion of the treating physician, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by either four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles.

    CRS-HIPEC is performed according to the Dutch protocol in all study centres.

    Interventions:
    • Other: Perioperative systemic therapy
    • Combination Product: Perioperative CAPOX-bevacizumab
    • Combination Product: Perioperative FOLFOX-bevacizumab
    • Combination Product: Perioperative FOLFIRI-bevacizumab
    • Procedure: CRS-HIPEC, experimental arm
  • Active Comparator: Upfront CRS-HIPEC alone
    CRS-HIPEC is performed according to the Dutch protocol in all study centres.
    Intervention: Procedure: CRS-HIPEC, control arm
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 5, 2017)
358
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2016)
340
Estimated Study Completion Date  ICMJE August 1, 2026
Estimated Primary Completion Date August 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Koen P Rovers, MD +31402396351 koen.rovers@catharinaziekenhuis.nl
Contact: Checca Bakkers, MD +31402396351 checca.bakkers@catharinaziekenhuis.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02758951
Other Study ID Numbers  ICMJE NL57644.100.16
2016-001865-99 ( EudraCT Number )
ISRCTN15977568 ( Registry Identifier: ISRCTN )
NTR6301 ( Registry Identifier: NTR )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The full protocol and Dutch informed consent forms are publicly accessible (https://dccg.nl/trial/cairo-6). Participant-level datasets and statistical codes will become available upon reasonable request after the results of the study have been published.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Analytic Code
Time Frame: The full protocol and Dutch informed consent forms are publicly accessible (https://dccg.nl/trial/cairo-6). Participant-level datasets and statistical codes will become available upon reasonable request after the results of the study have been published.
Access Criteria: Reasonable request.
URL: https://dccg.nl/trial/cairo-6
Responsible Party Koen Rovers, Catharina Ziekenhuis Eindhoven
Study Sponsor  ICMJE Koen Rovers
Collaborators  ICMJE
  • Dutch Cancer Society
  • Comprehensive Cancer Centre The Netherlands
  • Hoffmann-La Roche
Investigators  ICMJE
Study Chair: Ignace H de Hingh, MD, PhD Catharina Hospital, Eindhoven, Netherlands
Study Director: Pieter J Tanis, MD, PhD Department of Surgery, Amsterdam University Medical Centre, Location AMC, Amsterdam, Netherlands
Study Director: Cornelis J Punt, MD, PhD Department of Medical Oncology, Amsterdam University Medical Centre, Location AMC, Amsterdam, Netherlands
Principal Investigator: Alexandra R Brandt-Kerkhof, MD Department of Surgery, Erasmuc University Medical Centre, Rotterdam, Netherlands
Principal Investigator: Jurriaan B Tuynman, MD, PhD Department of Surgery, Amsterdam University Medical Centre, Location VUMC, Amsterdam, Netherlands
Principal Investigator: Arend G Aalbers, MD Department of Surgery, Netherlands Cancer Institute, Amsterdam, Netherlands
Principal Investigator: Marinus J Wiezer, MD, PhD Department of Surgery, St. Antonius Hospital, Nieuwegein, Netherlands
Principal Investigator: Patrick H Hemmer, MD Department of Surgery, University Medical Centre Groningen, Groningen, Netherlands
Principal Investigator: Sandra A Radema, MD, PhD Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, Netherlands
Principal Investigator: Wilhemina M van Grevenstein, MD, PhD Department of Surgery, University Medical Centre Utrecht, Utrecht, Netherlands
Principal Investigator: Eino B van Duyn, MD, PhD Department of Surgery, Medisch Spectrum Twente, Enschede, Netherlands
Principal Investigator: Ignace H de Hingh, MD, PhD Department of Surgery, Catharina Hospital, Eindhoven, Netherlands
PRS Account Catharina Ziekenhuis Eindhoven
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP