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Colon CancerPhase 3CAIRO4NCT01606098

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

A Phase 3 study testing Surgery of the primary tumour and Systemic treatment in people with Colon Cancer and Primary Tumour, run by Dutch Colorectal Cancer Group at 46 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Cancer, Primary Tumour, Rectal Cancer
What is being tested?
Surgery of the primary tumour and Systemic treatment
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
206 participants
Where
46 sitesin 2 countries
Study dates
Jul 2012to Dec 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

46 sites in 2 countries.

46 sites in 2 countries

Netherlands41 sites

  • Jeroen Bosch

    's-Hertogenbosch

  • Medisch Centrum Alkmaar

    Alkmaar

  • Ziekenhuisgroep Twente

    Almelo

  • Flevoziekenhuis

    Almere Stad

  • Ziekenhuis Amstelland

    Amstelveen

  • Academic Medical Centre

    Amsterdam

  • OLVG

    Amsterdam

  • VUMC

    Amsterdam

  • Gelre Ziekenhuis

    Apeldoorn

  • Wilhelmina Ziekenhuis

    Assen

  • Rode Kruis Ziekenhuis

    Beverwijk

  • Amphia Ziekenhuis

    Breda

  • Slingeland Ziekenhuis

    Doetinchem

  • Albert Schweitzer Ziekenhuis

    Dordrecht

  • Catharina Ziekenhuis

    Eindhoven

  • Maxima Medisch Centrum

    Eindhoven

  • St Annaziekenhuis

    Geldrop

  • Groene Hart Ziekenhuis

    Gouda

  • Martini Ziekenhuis

    Groningen

  • UMCG

    Groningen

  • Spaarne Gasthuis

    Haarlem

  • St Jansdal

    Harderwijk

  • Elkerliek Ziekenhuis

    Helmond

  • Spaarne Gasthuis

    Hoofddorp

  • St Antonius Ziekenhuis

    Nieuwegein

  • Radboudumc

    Nijmegen, 6542 KN

  • Waterland Ziekenhuis

    Purmerend

  • Laurentius Ziekenhuis

    Roermond

  • Maasstad Ziekenhuis

    Rotterdam, 3007 AC

  • Erasmus MC

    Rotterdam

  • Fransicus Gastuis & Vlietland

    Rotterdam

  • Antonius Ziekenhuis

    Sneek

  • MC Haaglanden en Bronovo Nebo

    The Hague

  • Ziekenhuis Rivierenland

    Tiel

  • Elisabeth-Tweesteden

    Tilburg

  • Bernhoven Ziekenhuis

    Uden

  • University Medical Centre Utrecht

    Utrecht

  • Bernhoven Ziekenhuis

    Veghel

  • VieCuri Medisch Centrum

    Venlo

  • Zaans Medisch Centrum

    Zaandam

  • Isala Klinieken

    Zwolle

Other trials in Netherlands

Denmark5 sites

  • University Hospital Aalborg

    Aalborg

  • Rigshospitalet

    Copenhagen

  • Herlev Hospital

    Herlev

  • Regionshospital Herning

    Herning

  • Roskilde hospital

    Roskilde

Other trials in Denmark

About this study

Official title: 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.

Being tested
Surgery of the primary tumour, Systemic treatment
Keywords
Surgery, Chemotherapy
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Surgery of the primary tumourProcedure or surgery

    Surgical resection of the colon tumour

  • Systemic treatmentDrug

    Also called Bevacizumab in combination with fluoropyrimidine-based schedules

    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)

Study groups in NCT01606098
Study groupRoleWhat they receive
Systemic treatmentActive comparatorFirst-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.
Receives: Drug: Systemic treatment
Surgery followed by systemic treatmentExperimentalSurgery 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
Receives: Procedure: Surgery of the primary tumour; Drug: Systemic treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Overall survival of the intent-to-treat population

    Measured: Time from randomisation until death, assessed up to 5 years

Secondary outcomes (9)

  1. Progression-free survival

    Measured: Time from randomisation until first progression or death whichever comes first, asessed up to 5 years

  2. Response to chemotherapy

    Response rate according to RECIST 1.1

    Measured: Fist-line chemotherapy, assessed until progression

  3. Systemic therapy related toxicity

    Adverse events grade 3-4 according to NCI-CTC 4.0

    Measured: Every 3 weeks during first-line treatment

  4. Surgery related morbidity and mortality

    Measured: 30 days

  5. Quality of life

    EORTC QLQ-C30 and CR38

    Measured: Every 6 months from randomisation until first progression

  6. Interval between randomization and initiation of systemic treatment

    Measured: Number of days between randomization and initiation of systemic treatment

  7. Cost-benefit analyses

    Measured: Until end of first-line systemic treatment

  8. Patients requiring resection of the primary tumour in the non-resection arm

    Number of patients requiring resection of the primary tumour in the non-resection arm

    Measured: Time from randomisation until death, assessed up to 5 years

  9. Overall survival in patients in whom treatment according to protocol was initiated

    Having received at least one cycle of systemic treatment in arm A and surgery in arm B

    Measured: Time form randomisation until death, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 May 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJun 2022
  4. Study completionDec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
206 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01606098
Sponsor's protocol ID
CAIRO4
Acronym
CAIRO4
Status last verified
Sep 2023
First submitted
23 May 2012
Last updated
13 Sep 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • van der Kruijssen DEW, Elias SG, van de Ven PM, van Rooijen KL, Lam-Boer J', Mol L, Punt CJA, Sommeijer DW, Tanis PJ, Nielsen JD, Yilmaz MK, van Riel JMGH, Wasowiz-Kemps DK, Loosveld OJL, van der Schelling GP, de Groot JWB, van Westreenen HL, Jakobsen HL, Fromm AL, Hamberg P, Verseveld M, Jaensch C, Liposits GI, van Duijvendijk P, Oulad Hadj J, van der Hoeven JAB, Trajkovic M, de Wilt JHW, Koopman M; CAIRO4 Working Group. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group. Ann Oncol. 2024 Sep;35(9):769-779. doi: 10.1016/j.annonc.2024.06.001. Epub 2024 Jun 7.

    PubMed 38852675

  • van der Kruijssen DEW, Elias SG, Vink GR, van Rooijen KL, 't Lam-Boer J, Mol L, Punt CJA, de Wilt JHW, Koopman M; CAIRO4 Working Group. Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment: The CAIRO4 Phase 3 Randomized Clinical Trial. JAMA Surg. 2021 Dec 1;156(12):1093-1101. doi: 10.1001/jamasurg.2021.4992.

    PubMed 34613339

  • 't Lam-Boer J, Mol L, Verhoef C, de Haan AF, Yilmaz M, Punt CJ, de Wilt JH, Koopman M. The CAIRO4 study: 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 of the Dutch Colorectal Cancer Group (DCCG). BMC Cancer. 2014 Oct 2;14:741. doi: 10.1186/1471-2407-14-741.

    PubMed 25277170

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Surgery of the primary tumour and Systemic treatment in people with Colon Cancer and Primary Tumour, run by Dutch Colorectal Cancer Group at 46 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in Netherlands, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: Time from randomisation until death, assessed up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01606098, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

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