Skip to main content
OpenTrials
Completed

NCT Number: NCT01606098

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Colon Cancer Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Primary Tumour Rectal Cancer Rectal Diseases Rectal Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University Hospital Aalborg, Aalborg, Denmark

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Surgery of the primary tumour

Procedure

Surgical resection of the colon tumour

Systemic treatment

Drug

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

Primary outcomes

  1. Overall survival

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

    Overall survival of the intent-to-treat population

Secondary outcomes

  1. Progression-free survival

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

  2. Response to chemotherapy

    Time frame: Fist-line chemotherapy, assessed until progression

    Response rate according to RECIST 1.1

  3. Systemic therapy related toxicity

    Time frame: Every 3 weeks during first-line treatment

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

  4. Surgery related morbidity and mortality

    Time frame: 30 days

  5. Quality of life

    Time frame: Every 6 months from randomisation until first progression

    EORTC QLQ-C30 and CR38

  6. Interval between randomization and initiation of systemic treatment

    Time frame: Number of days between randomization and initiation of systemic treatment

  7. Cost-benefit analyses

    Time frame: Until end of first-line systemic treatment

  8. 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

  9. 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

Sponsors and collaborators

Lead sponsor

Dutch Colorectal Cancer Group

Other

Collaborators

  • Hoffmann-La Roche

Registry information

Official study 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)

Acronym: CAIRO4

Important dates

Study start
2012
Primary completion
2022
Study completion
2022
First posted
May 25, 2012
Registry last updated
Sep 13, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.