The Role of Surgery of the Primary Tumour With Few or Absent Symptoms in Patients With Synchronous Unresectable Metastases of Colon Cancer (CAIRO4)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Dutch Colorectal Cancer Group
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier:
NCT01606098
First received: May 23, 2012
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Primary Tumour
Procedure: Surgery of the primary tumour
Drug: Systemic treatment (Bevacizumab in combination with fluoropyrimidine-based schedules)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Surgery of the Primary Tumour With Few or Absent Symptoms in Patients With Synchronous Unresectable Metastases of Colon Cancer, a Randomized Phase III Study

Resource links provided by NLM:


Further study details as provided by Dutch Colorectal Cancer Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Time from randomisation until death ] [ Designated as safety issue: No ]
    Overall survival of the intent-to-treat population


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from randomisation until first progression ] [ Designated as safety issue: No ]
    Time from randomisation until first progression or death whichever comes first

  • Response to chemotherapy [ Time Frame: Fist-line chemotherapy ] [ Designated as safety issue: No ]
    Response rate according to RECIST 1.1

  • Systemic therapy related toxicity [ Time Frame: During first-line treatment ] [ Designated as safety issue: Yes ]
    Adverse events grade 3-4 according to NCI-CTC 4.0

  • Surgery related morbidity and mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: From randomisation until first progression ] [ Designated as safety issue: No ]
    EORTC QLQ-C30 and CR38

  • Interval between randomization and initiation of systemic treatment [ Time Frame: Number of days between randomization and initiation of systemic treatment ] [ Designated as safety issue: No ]
  • Cost-benefit analyses [ Time Frame: Until end of first-line systemic treatment ] [ Designated as safety issue: No ]
  • Patients requiring resection of the primary tumour in the non-resection arm [ Designated as safety issue: No ]
    Number of patients requiring resection of the primary tumour in the non-resection arm

  • Overall survival [ Time Frame: Time from randomisation until death ] [ Designated as safety issue: No ]
    Overall survival in patients in treatment according to protocol was initiated


Estimated Enrollment: 360
Study Start Date: July 2012
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 (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)

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
Procedure: Surgery of the primary tumour
Surgical resection of the colon tumour
Drug: Systemic treatment (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)


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological proof of colon cancer
  • Resectable primary tumour in situ with unresectable distant metastases
  • 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
  • Rectal cancer
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01606098

Contacts
Contact: Linda Mol, MSc 00312416837 l.mol@iknl.nl

Locations
Netherlands
Medisch Centrum Alkmaar Recruiting
Alkmaar, Netherlands
Principal Investigator: C H Smorenburg, MD, PhD         
Ziekenhuisgroep Twente Recruiting
Almelo, Netherlands
Principal Investigator: E. Kouwenhoven         
Amsterdam Medical Centre Recruiting
Amsterdam, Netherlands
Principal Investigator: B. C. Tanis, MD, PhD         
OLVG Recruiting
Amsterdam, Netherlands
Principal Investigator: B de Valk, MD, PhD         
VUMC Recruiting
Amsterdam, Netherlands
Principal Investigator: H. Verheul, Prof. MD         
Wilhelmina Ziekenhuis Recruiting
Assen, Netherlands
Principal Investigator: P J Nieboer, MD         
Ziekenhuis Lievensberg Recruiting
Bergen op Zoom, Netherlands
Principal Investigator: M Troost         
Rode Kruis Ziekenhuis Recruiting
Beverwijk, Netherlands
Principal Investigator: R. C. Rietbroek, MD, PhD         
Tergooiziekenhuizen Not yet recruiting
Blaricum, Netherlands
Principal Investigator: S Luyx- de Bakker         
Amphia Ziekenhuis Not yet recruiting
Breda, Netherlands
Principal Investigator: O Loosveld         
Principal Investigator: Schelling         
Ommelander loc. Delfzicht Recruiting
Delfzijl, Netherlands
Principal Investigator: Z. Erjavec         
Deventer Ziekenhuis Recruiting
Deventer, Netherlands
Principal Investigator: A LT Imholz, MD, PhD         
Slingeland Ziekenhuis Recruiting
Doetinchem, Netherlands
Principal Investigator: Erik Muller, MD, PhD         
Albert Schweitzer Ziekenhuis Not yet recruiting
Dordrecht, Netherlands
Ziekenhuis Nij Smellinghe Recruiting
Drachten, Netherlands
Principal Investigator: S. Hovenga, MD         
Catherina Ziekenhuis Recruiting
Eindhoven, Netherlands
Principal Investigator: I HJ de Hingh, MD, PhD         
Sub-Investigator: G J Creemers, MD, PhD         
Medisch Spectrum Twente Not yet recruiting
Enschede, Netherlands
Principal Investigator: M CJ Legdeur, MD, PhD         
Sub-Investigator: W Mastboom         
UMCG Recruiting
Groningen, Netherlands
Principal Investigator: K. Havenga         
Martini Ziekenhuis Recruiting
Groningen, Netherlands
Principal Investigator: R S de Jong, MD, PhD         
Kennemer Gasthuis Not yet recruiting
Haarlem, Netherlands
Principal Investigator: Stockmann, MD         
St Jansdal Recruiting
Harderwijk, Netherlands
Principal Investigator: M. Temizkan         
Atrium Medisch Centrum Recruiting
Heerlen, Netherlands
Principal Investigator: F. van de Berkmortel, MD, PhD         
Elkerliek Ziekenhuis Recruiting
Helmond, Netherlands
Principal Investigator: V. Derleyn, MD, PhD         
Sub-Investigator: J A Wegman, MD, PhD         
St Annaziekenhuis Recruiting
Helmond, Netherlands
Principal Investigator: A E Smals         
Spaarne Ziekenhuis Recruiting
Hoofddorp, Netherlands
Principal Investigator: CAM de Swart, MD, PhD         
Medisch Centrum Leeuwarden Recruiting
Leeuwarden, Netherlands
Principal Investigator: M.B. Polee         
Antonius Ziekenhuis Recruiting
Nieuwegein, Netherlands
Principal Investigator: M Los         
Canisius Wilhelmina Ziekenhuis Not yet recruiting
Nijmegen, Netherlands
Principal Investigator: B. ME Hansson, MD, PhD         
Sub-Investigator: C. Mandigers, MD, PhD         
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands, 6542 KN
Principal Investigator: J HW de Wilt, Prof.         
Sub-Investigator: C. van Herpen, MD, PhD         
Bernhoven Ziekenhuis Recruiting
Oss, Netherlands
Principal Investigator: J van Hoogstraten, MD, PhD         
Waterland Ziekenhuis Recruiting
Purmerend, Netherlands
Principal Investigator: J. A.C Brakenhof, MD         
St Franciscus Gasthuis Recruiting
Rotterdam, Netherlands
Contact: P. Hamberg, MD         
Principal Investigator: P. Hamberg, MD         
Vlietland Ziekenhuis Recruiting
Schiedam, Netherlands
Principal Investigator: J J Braun, MD         
Orbis Medisch Centrum Recruiting
Sittard, Netherlands
Principal Investigator: F.L.G. Erdkamp, MD, PhD         
Antonius Ziekenhuis Recruiting
Sneek, Netherlands
Principal Investigator: D A Hess, MD         
Ziekenhuis Rivierenland Recruiting
Tiel, Netherlands
Principal Investigator: M. Tjin-a-Ton, MD         
Tweesteden Ziekenhuis Recruiting
Tilburg, Netherlands
Principal Investigator: H.T.J. Roerdink, MD         
St Elisabeth Recruiting
Tilburg, Netherlands
Principal Investigator: J van Riel         
University Medical Centre Utrecht Not yet recruiting
Utrecht, Netherlands
Sub-Investigator: M Koopman, MD, PhD         
Principal Investigator: W MU van Grevenstein, MD, PhD         
Bernhoven Ziekenhuis Recruiting
Veghel, Netherlands
Principal Investigator: J van Hoogstraten, MD, PhD         
VieCuri Medisch Centrum Recruiting
Venlo, Netherlands
Principal Investigator: Y van de Wouw, MD, PhD         
Sint Jansgasthuis Recruiting
Weert, Netherlands
Principal Investigator: N.A.J.B. Peters         
Zaans Medisch Centrum Recruiting
Zaandam, Netherlands
Principal Investigator: A Bochove         
Sponsors and Collaborators
Dutch Colorectal Cancer Group
Hoffmann-La Roche
Investigators
Principal Investigator: M. Koopman, MD, PhD University Medical Centre Utrecht
Principal Investigator: H. J.W. de Wilt, Prof. MD. PhD. Radboud University
  More Information

Additional Information:
No publications provided

Responsible Party: Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier: NCT01606098     History of Changes
Other Study ID Numbers: CAIRO4
Study First Received: May 23, 2012
Last Updated: June 24, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Dutch Colorectal Cancer Group:
Surgery
Chemotherapy

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014