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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 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: July 15, 2015
Last verified: July 2015
  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
Rectal Cancer
Procedure: Surgery of the primary tumour
Drug: Systemic treatment
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 Colorectal Cancer, a Randomized Phase III Study. A Study of the Dutch Colorectal Cancer Group (DCCG)

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 [ Time Frame: Time from randomisation until death ] [ 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 Study Completion Date: August 2020
Estimated Primary Completion Date: August 2018 (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

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

  Eligibility

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

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
  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: Jorine 't Lam-Boer, MSc jorine.tLam-Boer@radboudumc.nl
Contact: Linda Mol l.mol@iknl.nl

  Show 51 Study Locations
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 by Dutch Colorectal Cancer Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: July 15, 2015
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:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015