The Role of Surgery of the Primary Tumour in Patients With Synchronous Unresectable Metastases of Colorectal Cancer (CAIRO4)

September 11, 2023 updated by: Dutch Colorectal Cancer Group

The Role of Surgery of the Primary Tumour With Few or Absent Symptoms in Patients With Synchronous Unresectable Metastases of Colorectal Cancer, a Randomized Phase III Study. A Study of the Dutch Colorectal Cancer Group (DCCG)

The clinical benefit of resection of the primary tumour in patients with synchronous unresectable metastases is not known. In the literature studies usually describe retrospective selected patients with synchronous metastases treated with or without resection of the primary tumour. All these studies are biased in patient selection and there are no prospective randomized studies on this topic. In patients with few or absent symptoms of the primary tumour, arguments both in favour and against initial resection have been presented, and therefore a randomized trial is warranted. Although recent publications suggest that resection of the primary tumour in synchronous metastasized colon cancer patients might not be necessary, this appears to be based on feasibility and not on clinical outcome. Several studies comparing large groups of patients with or without resection of the primary tumour suggest an improved survival when the primary tumour is resected. A potential benefit of resection of the primary tumour is to prevent complications of the primary tumour during chemotherapy treatment or during later stages of the disease. A recent analysis of the CAIRO and CAIRO2 data showed that metastatic colon cancer patients who had a resection of the primary tumour prior to study entry, had an improved survival compared to patients without a resection of the primary tumour. However, these patients were selected after the primary tumour was resected and therefore these results are not corrected for surgical morbidity and mortality. The investigators here propose a randomized trial in order to demonstrate that resection of the primary tumour does improve overall survival.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
206

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aalborg, Denmark
        • University Hospital Aalborg
      • Copenhagen, Denmark
        • Rigshospitalet
      • Herlev, Denmark
        • Herlev Hospital
      • Herning, Denmark
        • Regionshospital Herning
      • Roskilde, Denmark
        • Roskilde Hospital
  • Netherlands
      • Alkmaar, Netherlands
        • Medisch Centrum Alkmaar
      • Almelo, Netherlands
        • Ziekenhuisgroep Twente
      • Almere, Netherlands
        • Flevoziekenhuis
      • Amstelveen, Netherlands
        • Ziekenhuis Amstelland
      • Amsterdam, Netherlands
        • Academic Medical Centre
      • Amsterdam, Netherlands
        • OLVG
      • Amsterdam, Netherlands
        • VUMC
      • Apeldoorn, Netherlands
        • Gelre Ziekenhuis
      • Assen, Netherlands
        • Wilhelmina ziekenhuis
      • Beverwijk, Netherlands
        • Rode Kruis Ziekenhuis
      • Breda, Netherlands
        • Amphia Ziekenhuis
      • Den Bosch, Netherlands
        • Jeroen Bosch
      • Den Haag, Netherlands
        • MC Haaglanden en Bronovo Nebo
      • Doetinchem, Netherlands
        • Slingeland Ziekenhuis
      • Dordrecht, Netherlands
        • Albert Schweitzer Ziekenhuis
      • Eindhoven, Netherlands
        • Catharina Ziekenhuis
      • Eindhoven, Netherlands
        • Maxima Medisch Centrum
      • Geldrop, Netherlands
        • St Annaziekenhuis
      • Gouda, Netherlands
        • Groene Hart Ziekenhuis
      • Groningen, Netherlands
        • Martini ziekenhuis
      • Groningen, Netherlands
        • UMCG
      • Haarlem, Netherlands
        • Spaarne Gasthuis
      • Harderwijk, Netherlands
        • St Jansdal
      • Helmond, Netherlands
        • Elkerliek Ziekenhuis
      • Hoofddorp, Netherlands
        • Spaarne Gasthuis
      • Nieuwegein, Netherlands
        • St Antonius Ziekenhuis
      • Nijmegen, Netherlands, 6542 KN
        • Radboudumc
      • Purmerend, Netherlands
        • Waterland Ziekenhuis
      • Roermond, Netherlands
        • Laurentius ziekenhuis
      • Rotterdam, Netherlands
        • Erasmus MC
      • Rotterdam, Netherlands, 3007 AC
        • Maasstad ziekenhuis
      • Rotterdam, Netherlands
        • Fransicus Gastuis & Vlietland
      • Sneek, Netherlands
        • Antonius ziekenhuis
      • Tiel, Netherlands
        • Ziekenhuis Rivierenland
      • Tilburg, Netherlands
        • Elisabeth-TweeSteden
      • Uden, Netherlands
        • Bernhoven Ziekenhuis
      • Utrecht, Netherlands
        • University Medical Centre Utrecht
      • Veghel, Netherlands
        • Bernhoven Ziekenhuis
      • Venlo, Netherlands
        • VieCuri Medisch Centrum
      • Zaandam, Netherlands
        • Zaans Medisch Centrum
      • Zwolle, Netherlands
        • Isala Klinieken

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histological proof of colorectal cancer
  • Resectable primary tumour in situ with unresectable distant metastases
  • No indication for neo-adjuvant (chemo)radiation
  • No severe signs or symptoms related to the primary tumour (i.e. severe bleeding, obstruction, severe abdominal pain) that require immediate surgery or other symptomatic treatment (e.g. stenting)
  • No prior systemic treatment for advanced disease
  • Age ≥ 18 years
  • WHO performance status 0-2
  • Laboratory values obtained ≤ 4 weeks prior to randomization: Adequate bone marrow function (Hb ≥ 6.0 mmol/L, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, ≥ 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases)
  • Expected adequacy of follow-up
  • Written informed consent
  • CT scan abdomen and CT thorax/X-thorax performed ≤ 4 weeks prior to randomization

Exclusion Criteria:

  • Pregnancy, lactation
  • Unresectable primary tumour (i.e. neurovascular encasement, substantial ingrowth in pancreatic head), or any condition preventing the safety or feasibility of resection of the primary tumour, i.e. massive ascites or extensive peritoneal disease
  • Requirement of neoadjuvant (chmo)radiation therapy
  • Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin
  • Any medical condition that prevents the safe administration of systemic treatment
  • Previous intolerance of fluoropyrimidines, known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Planned radical resection of all metastatic disease
  • Uncontrolled hypertension, i.e. values consistently > 150/100 mmHg
  • Use of ≥ 3 antihypertensive drugs
  • Significant cardiovascular disease < 1 yr before randomization (symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, cerebro vascular event)
  • Chronic active infection
  • Concurrent treatment with any other anti-cancer therapy as described per protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Systemic treatment
First-line fluoropyrimidine-based chemotherapy with bevacizumab initiated within 4 weeks of randomization, followed by salvage therapy upon progression at the discretion of the local investigator. Surgery of primary tumour will be performed only when indicated by local signs or symptoms.
Drug: Systemic treatment

First line fluoropyrimidine-based chemotherapy with bevacizumab. The chemotherapy regimen is to the discretion of the local investigator, who may choose between:

5FU/LV or capecitabine or capecitabine + oxaliplatin(CAPOX)or 5FU + oxaliplatin(FOLFOX 4 or FOLFOX 7)or 5FU + irinotecan (FOLFIRI) or capecitabine + irinotecan(CAPIRI)

Other Names:
  • Bevacizumab in combination with fluoropyrimidine-based schedules
Experimental: Surgery followed by systemic treatment
Surgery within 4 weeks of randomization followed by fluoropyrimidine-based chemotherapy with bevacizumab until progression or unacceptable toxicity, followed by salvage therapy upon progression at the discretion of the local investigator
Drug: Systemic treatment

First line fluoropyrimidine-based chemotherapy with bevacizumab. The chemotherapy regimen is to the discretion of the local investigator, who may choose between:

5FU/LV or capecitabine or capecitabine + oxaliplatin(CAPOX)or 5FU + oxaliplatin(FOLFOX 4 or FOLFOX 7)or 5FU + irinotecan (FOLFIRI) or capecitabine + irinotecan(CAPIRI)

Other Names:
  • Bevacizumab in combination with fluoropyrimidine-based schedules
Procedure: Surgery of the primary tumour
Surgical resection of the colon tumour

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Time from randomisation until death, assessed up to 5 years
Overall survival of the intent-to-treat population
Time from randomisation until death, assessed up to 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: Time from randomisation until first progression or death whichever comes first, asessed up to 5 years
Time from randomisation until first progression or death whichever comes first, asessed up to 5 years
Response to chemotherapy
Time Frame: Fist-line chemotherapy, assessed until progression
Response rate according to RECIST 1.1
Fist-line chemotherapy, assessed until progression
Systemic therapy related toxicity
Time Frame: Every 3 weeks during first-line treatment
Adverse events grade 3-4 according to NCI-CTC 4.0
Every 3 weeks during first-line treatment
Surgery related morbidity and mortality
Time Frame: 30 days
30 days
Quality of life
Time Frame: Every 6 months from randomisation until first progression
EORTC QLQ-C30 and CR38
Every 6 months from randomisation until first progression
Interval between randomization and initiation of systemic treatment
Time Frame: Number of days between randomization and initiation of systemic treatment
Number of days between randomization and initiation of systemic treatment
Cost-benefit analyses
Time Frame: Until end of first-line systemic treatment
Until end of first-line systemic treatment
Patients requiring resection of the primary tumour in the non-resection arm
Time Frame: Time from randomisation until death, assessed up to 5 years
Number of patients requiring resection of the primary tumour in the non-resection arm
Time from randomisation until death, assessed up to 5 years
Overall survival in patients in whom treatment according to protocol was initiated
Time Frame: Time form randomisation until death, assessed up to 5 years
Having received at least one cycle of systemic treatment in arm A and surgery in arm B
Time form randomisation until death, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dutch Colorectal Cancer Group

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: M. Koopman, Prof MD PhD, UMC Utrecht
  • Principal Investigator: H. JW de Wilt, Prof MD PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2012

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 25, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAIRO4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings