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

Primary Purpose

Colorectal Neoplasm, Colorectal Cancer, Colorectal Neoplasms Malignant

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Perioperative systemic therapy
Perioperative CAPOX-bevacizumab
Perioperative FOLFOX-bevacizumab
Perioperative FOLFIRI-bevacizumab
CRS-HIPEC, experimental arm
CRS-HIPEC, control arm
Sponsored by
Koen Rovers
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Neoplasm focused on measuring Colorectal Neoplasms, Peritoneal Neoplasms, Cytoreduction Surgical Procedures, Hyperthermia, Induced, Neoadjuvant Therapy, Adjuvant Chemotherapy, Bevacizumab, Randomized Controlled Trial, Mortality, Progression-Free Survival

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ziekenhuis Oost-LimburgRecruiting
  • Amsterdam University Medical Centre, Location VUMCRecruiting
  • Netherlands Cancer InstituteRecruiting
  • Catharina HospitalRecruiting
  • University Medical Centre GroningenRecruiting
  • St. Antonius HospitalRecruiting
  • Radboud University Medical CentreRecruiting
  • Erasmus University Medical CentreRecruiting
  • University Medical Centre UtrechtRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Perioperative systemic therapy and CRS-HIPEC

Upfront CRS-HIPEC alone

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Phase II (n=80): feasibility of perioperative systemic therapy (1)
Number of patients that start neoadjuvant systemic therapy
Phase II (n=80): feasibility of perioperative systemic therapy (2)
Number of patients that complete neoadjuvant systemic therapy
Phase II (n=80): feasibility of perioperative systemic therapy (3)
Number of patients with a dose reduction during neoadjuvant systemic therapy
Phase II (n=80): feasibility of perioperative systemic therapy (4)
Number of patients that are scheduled for CRS-HIPEC
Phase II (n=80): feasibility of perioperative systemic therapy (5)
Number of patients that undergo complete CRS-HIPEC
Phase II (n=80): feasibility of perioperative systemic therapy (6)
Number of patients that start adjuvant systemic therapy
Phase II (n=80): feasibility of perioperative systemic therapy (7)
Number of patients that complete adjuvant systemic therapy
Phase II (n=80): feasibility of perioperative systemic therapy (8)
Number of patients with a dose reduction during adjuvant systemic therapy
Phase II (n=80): safety of perioperative systemic therapy (1)
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)
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)
EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) during the initial treatment
Phase II (n=80): tolerance of perioperative systemic therapy (2)
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)
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
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
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 between randomisation and death
Phase III (n=358): progression-free survival
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 between CRS-HIPEC and radiological proof of recurrence or death in operated patients
Phase III (n=358): health-related quality of life (1)
EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)
Phase III (n=358): health-related quality of life (2)
European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire C30
Phase III (n=358): health-related quality of life (3)
European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire CR29
Phase III (n=358): costs (1)
Institute for Medical Technology Assessment Productivity Cost Questionnaire
Phase III (n=358): costs (2)
Institute for Medical Technology Assessment Medical Consumption Questionnaire
Phase III (n=358): major postoperative morbidity
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
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
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
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.

Secondary Outcome Measures

Full Information

First Posted
April 26, 2016
Last Updated
February 8, 2023
Sponsor
Koen Rovers
Collaborators
Dutch Cancer Society, Comprehensive Cancer Centre The Netherlands, Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02758951
Brief Title
Perioperative Systemic Therapy for Isolated Resectable Colorectal Peritoneal Metastases
Acronym
CAIRO6
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2017 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Koen Rovers
Collaborators
Dutch Cancer Society, Comprehensive Cancer Centre The Netherlands, Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Colorectal Neoplasms, Peritoneal Neoplasms, Cytoreduction Surgical Procedures, Hyperthermia, Induced, Neoadjuvant Therapy, Adjuvant Chemotherapy, Bevacizumab, Randomized Controlled Trial, Mortality, Progression-Free Survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
358 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Perioperative systemic therapy and CRS-HIPEC
Arm Type
Experimental
Arm Description
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.
Arm Title
Upfront CRS-HIPEC alone
Arm Type
Active Comparator
Arm Description
CRS-HIPEC is performed according to the Dutch protocol in all study centres.
Intervention Type
Other
Intervention Name(s)
Perioperative systemic therapy
Intervention Description
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.
Intervention Type
Combination Product
Intervention Name(s)
Perioperative CAPOX-bevacizumab
Intervention Description
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.
Intervention Type
Combination Product
Intervention Name(s)
Perioperative FOLFOX-bevacizumab
Intervention Description
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.
Intervention Type
Combination Product
Intervention Name(s)
Perioperative FOLFIRI-bevacizumab
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
CRS-HIPEC, experimental arm
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
CRS-HIPEC, control arm
Intervention Description
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.
Primary Outcome Measure Information:
Title
Phase II (n=80): feasibility of perioperative systemic therapy (1)
Description
Number of patients that start neoadjuvant systemic therapy
Time Frame
Approximately one month after randomisation
Title
Phase II (n=80): feasibility of perioperative systemic therapy (2)
Description
Number of patients that complete neoadjuvant systemic therapy
Time Frame
Approximately four months after randomisation
Title
Phase II (n=80): feasibility of perioperative systemic therapy (3)
Description
Number of patients with a dose reduction during neoadjuvant systemic therapy
Time Frame
Approximately four months after randomisation
Title
Phase II (n=80): feasibility of perioperative systemic therapy (4)
Description
Number of patients that are scheduled for CRS-HIPEC
Time Frame
Approximately five months after randomisation
Title
Phase II (n=80): feasibility of perioperative systemic therapy (5)
Description
Number of patients that undergo complete CRS-HIPEC
Time Frame
Approximately five months after randomisation
Title
Phase II (n=80): feasibility of perioperative systemic therapy (6)
Description
Number of patients that start adjuvant systemic therapy
Time Frame
Approximately eight months after randomisation
Title
Phase II (n=80): feasibility of perioperative systemic therapy (7)
Description
Number of patients that complete adjuvant systemic therapy
Time Frame
Approximately eleven months after randomisation
Title
Phase II (n=80): feasibility of perioperative systemic therapy (8)
Description
Number of patients with a dose reduction during adjuvant systemic therapy
Time Frame
Approximately eleven months after randomisation
Title
Phase II (n=80): safety of perioperative systemic therapy (1)
Description
Number of patients with systemic related toxicity, defined as grade 2 or higher according to CTCAE v4.0
Time Frame
Up to one month after the last administration of systemic therapy (approximately one year after randomisation)
Title
Phase II (n=80): safety of perioperative systemic therapy (2)
Description
Number of patients with postoperative morbidity, defined as grade 2 or higher according to Clavien-Dindo
Time Frame
Up to three months after CRS-HIPEC (approximately eight months after randomisation)
Title
Phase II (n=80): tolerance of perioperative systemic therapy (1)
Description
EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) during the initial treatment
Time Frame
Up to six months after CRS-HIPEC (approximately eleven months after randomisation)
Title
Phase II (n=80): tolerance of perioperative systemic therapy (2)
Description
European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire C30 during the initial treatment
Time Frame
Up to six months after CRS-HIPEC (approximately eleven months after randomisation)
Title
Phase II (n=80): tolerance of perioperative systemic therapy (3)
Description
European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire CR29 during the initial treatment
Time Frame
Up to six months after CRS-HIPEC (approximately eleven months after randomisation)
Title
Phase II (n=80): radiological response of colorectal PM to neoadjuvant systemic therapy
Description
Number of patients with an objective radiological response. Central review of thoracoabdominal CT during neoadjuvant systemic therapy. Classification not defined a priori.
Time Frame
Approximately three months after randomisation
Title
Phase II (n=80): histological response of colorectal PM to neoadjuvant systemic therapy
Description
Number of patients with an objective histological response. Central review of specimens resected during CRS-HIPEC. Classification not defined a priori.
Time Frame
Approximately five months after randomisation
Title
Phase III (n=358): overall survival
Description
Time between randomisation and death
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): progression-free survival
Description
Time between randomisation and disease progression before CRS-HIPEC, CRS-HIPEC in case of unresectable disease, radiological proof of recurrence, or death
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): disease-free survival
Description
Time between CRS-HIPEC and radiological proof of recurrence or death in operated patients
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): health-related quality of life (1)
Description
EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): health-related quality of life (2)
Description
European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire C30
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): health-related quality of life (3)
Description
European Organisation for Research and Treatment of Cancer Qualify of Life Questionnaire CR29
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): costs (1)
Description
Institute for Medical Technology Assessment Productivity Cost Questionnaire
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): costs (2)
Description
Institute for Medical Technology Assessment Medical Consumption Questionnaire
Time Frame
Up to five years after randomisation
Title
Phase III (n=358): major postoperative morbidity
Description
Number of patients with postoperative morbidity, defined as grade 2 or higher according to Clavien-Dindo
Time Frame
Up to three months after CRS-HIPEC (approximately eight months after randomisation)
Title
Phase III (n=358): major systemic therapy related toxicity
Description
Number of patients with systemic related toxicity, defined as grade 2 or higher according to CTCAE v4.0
Time Frame
Up to one month after the last administration of systemic therapy (approximately one year after randomisation)
Title
Phase III (n=358): radiological response of colorectal PM to neoadjuvant systemic therapy
Description
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
Time Frame
Approximately three months after randomisation
Title
Phase III (n=358): histological response of colorectal PM to neoadjuvant systemic therapy
Description
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.
Time Frame
Approximately five months after randomisation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Koen P Rovers, MD
Phone
+31402396351
Email
koen.rovers@catharinaziekenhuis.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Checca Bakkers, MD
Phone
+31402396351
Email
checca.bakkers@catharinaziekenhuis.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ignace H de Hingh, MD, PhD
Organizational Affiliation
Catharina Hospital, Eindhoven, Netherlands
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Pieter J Tanis, MD, PhD
Organizational Affiliation
Department of Surgery, Amsterdam University Medical Centre, Location AMC, Amsterdam, Netherlands
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Cornelis J Punt, MD, PhD
Organizational Affiliation
Department of Medical Oncology, Amsterdam University Medical Centre, Location AMC, Amsterdam, Netherlands
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Alexandra R Brandt-Kerkhof, MD
Organizational Affiliation
Department of Surgery, Erasmuc University Medical Centre, Rotterdam, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jurriaan B Tuynman, MD, PhD
Organizational Affiliation
Department of Surgery, Amsterdam University Medical Centre, Location VUMC, Amsterdam, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Arend G Aalbers, MD
Organizational Affiliation
Department of Surgery, Netherlands Cancer Institute, Amsterdam, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marinus J Wiezer, MD, PhD
Organizational Affiliation
Department of Surgery, St. Antonius Hospital, Nieuwegein, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Patrick H Hemmer, MD
Organizational Affiliation
Department of Surgery, University Medical Centre Groningen, Groningen, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sandra A Radema, MD, PhD
Organizational Affiliation
Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wilhemina M van Grevenstein, MD, PhD
Organizational Affiliation
Department of Surgery, University Medical Centre Utrecht, Utrecht, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eino B van Duyn, MD, PhD
Organizational Affiliation
Department of Surgery, Medisch Spectrum Twente, Enschede, Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ignace H de Hingh, MD, PhD
Organizational Affiliation
Department of Surgery, Catharina Hospital, Eindhoven, Netherlands
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ziekenhuis Oost-Limburg
City
Genk
State/Province
Vlaanderen
ZIP/Postal Code
3600
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kurt van der Speeten, Prof. dr.
Phone
+3289325050
Email
kurt.vanderspeeten@zol.be
First Name & Middle Initial & Last Name & Degree
Marga Bogaert
Phone
+3289326026
Email
marga.bogaert@zol.be
First Name & Middle Initial & Last Name & Degree
Kurt van der Speeten, prof. dr.
First Name & Middle Initial & Last Name & Degree
Marga Bogaert
Facility Name
Amsterdam University Medical Centre, Location VUMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jurriaan B Tuynman, MD, PhD
Phone
+31204444444
Email
j.tuynman@vumc.nl
First Name & Middle Initial & Last Name & Degree
Henk M Verheul, MD, PhD
Phone
+31204444444
Email
h.verheul@vumc.nl
First Name & Middle Initial & Last Name & Degree
Jurriaan B Tuynman, MD, PhD
First Name & Middle Initial & Last Name & Degree
Henk M Verheul, MD, PhD
Facility Name
Netherlands Cancer Institute
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arend G Aalbers, MD
Phone
+31205129111
Email
a.aalbers@nki.nl
First Name & Middle Initial & Last Name & Degree
Myriam Chalabi, MD
Phone
+31205129111
Email
m.chalabi@nki.nl
First Name & Middle Initial & Last Name & Degree
Arend G Aalbers, MD
First Name & Middle Initial & Last Name & Degree
Myriam Chalabi, MD
Facility Name
Catharina Hospital
City
Eindhoven
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ignace H de Hingh, MD, PhD
Phone
+31402397150
Email
ignace.d.hingh@catharinaziekenhuis.nl
First Name & Middle Initial & Last Name & Degree
Geert-Jan M Creemers, MD, PhD
Phone
+31402396622
Email
geert-jan.creemers@catharinaziekenhuis.nl
First Name & Middle Initial & Last Name & Degree
Ignace H de Hingh, MD, PhD
First Name & Middle Initial & Last Name & Degree
Geert-Jan M Creemers, MD, PhD
Facility Name
University Medical Centre Groningen
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick H Hemmer, MD
Phone
+31503616161
Email
p.h.j.hemmer@umcg.nl
First Name & Middle Initial & Last Name & Degree
Derk Jan A de Groot, MD, PhD
Phone
+31503616161
Email
d.j.a.de.groot@umcg.nl
First Name & Middle Initial & Last Name & Degree
Patrick H Hemmer, MD
First Name & Middle Initial & Last Name & Degree
Derk Jan A de Groot, MD, PhD
Facility Name
St. Antonius Hospital
City
Nieuwegein
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marinus J Wiezer, MD, PhD
Phone
+31883201900
Email
r.wiezer@antoniusziekenhuis.nl
First Name & Middle Initial & Last Name & Degree
Maartje Los, MD, PhD
Phone
+31883205700
Email
m.los@antoniusziekenhuis.nl
First Name & Middle Initial & Last Name & Degree
Marinus J Wiezer, MD, PhD
First Name & Middle Initial & Last Name & Degree
Maartje Los, MD, PhD
Facility Name
Radboud University Medical Centre
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra A Radema, MD, PhD
Phone
+31243618800
Email
sandra.radema@radboudumc.nl
First Name & Middle Initial & Last Name & Degree
Johannes H de Wilt, MD, PhD
Phone
+31243613808
Email
hans.dewilt@radboudumc.nl
First Name & Middle Initial & Last Name & Degree
Sandra A Radema, MD, PhD
First Name & Middle Initial & Last Name & Degree
Johannes H de Wilt, MD, PhD
Facility Name
Erasmus University Medical Centre
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra R Brandt-Kerkhof, MD
Phone
+31107041506
Email
a.brandt-kerkhof@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Esther van Meerten, MD, PhD
Phone
+31107040704
Email
e.vanmeerten@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Alexandra R Brandt-Kerkhof, MD
First Name & Middle Initial & Last Name & Degree
Esther van Meerten, MD, PhD
Facility Name
University Medical Centre Utrecht
City
Utrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wilhelmina M van Grevenstein, MD, PhD
Phone
+31887556901
Email
w.m.u.vangrevenstein@umcutrecht.nl
First Name & Middle Initial & Last Name & Degree
Miriam Koopman, MD, PhD
Phone
+31887556308
Email
m.koopman-6@umcutrecht.nl
First Name & Middle Initial & Last Name & Degree
Wilhelmina M van Grevenstein, MD, PhD
First Name & Middle Initial & Last Name & Degree
Miriam Koopman, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing Access Criteria
Reasonable request.
IPD Sharing URL
https://dccg.nl/trial/cairo-6
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Perioperative Systemic Therapy for Isolated Resectable Colorectal Peritoneal Metastases

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