A Randomised Trial of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC)

May 9, 2023 updated by: University College, London

Patients who have been treated successfully for bowel cancer (colorectal cancer) sometimes go on to develop nodules of disease in another part of the body. If this disease is found to be related to the original cancer it is called a metastasis. Some patients develop one or more metastases particularly in the lungs or the liver.

There is a growing trend to remove lung metastases with an operation, in the belief that this will help patients live longer, however there have not been any scientific studies to prove this. There is also very little published information about the side effects of this surgery and how it affects subsequent daily living. This is a feasibility study to determine whether it will be possible to conduct a large randomised controlled trial investigating the value of pulmonary metastasectomy (surgery to remove lung metastases) in patients who have been successfully treated for colorectal cancer. There is a two stage consent and randomisation process. Firstly, patients will be invited to consent to having a full range of investigations to assess their suitability for surgery. If found to be suitable, they will then be invited to consent to randomisation between active monitoring of their disease or active monitoring with pulmonary metastasectomy. Patients will be followed up regularly for 5 years to assess their disease status and to measure their quality of life and lung function.

Study Overview

Detailed Description

Colorectal cancer is one of the three commonest solid tumours. Approximately 100 cases are diagnosed each day in the UK. In 2006, 37,514 cases of colorectal cancer were diagnosed.

The increasing use of CT scans in routine follow up of patients has led to earlier diagnosis of isolated and/or subclinical lung nodules and there has been widespread adoption of pulmonary metastasectomy in selected cases. A survey of practice in Europe showed that pulmonary metastasectomy is very commonly performed but criteria vary widely. About 300 such operations were being carried out annually in the UK when PulMiCC opened as a 'feasibility' study.

Although well-established in clinical practice there have been no previous randomised controlled trials of the effect of lung metastasectomy on survival and there is doubt as to its clinical effectiveness. The most recent systematic review and meta-analysis concludes that pulmonary metastasectomy is associated with a high likelihood of recurrence, with doubling of the recurrence rate with each of three adverse prognostic factors: (i) more than one metastasis, (ii) an interoperative interval (primary resection to lung metastasectomy) less than three years, (iii) elevated CEA.

In a prospective registry capturing more than 60% of Spanish practice for a two year period these limits were commonly exceeded.

In an RCT it has been shown that recurrence can be detected earlier with CT and/or CEA surveillance and as a result more liver and lung metastasectomy operations were performed. However, these operations did not provide any survival benefit, within the RCT. The uncertainty about the practice has been set out in the British Medical Journal in 2014.

Pulmonary metastasectomy is thus part of a bigger question about effectiveness of surgery for metastases from colorectal cancer.

There are known unfavourable prognostic factors which include the number of metastases and the length of time they take to become evident radiologically: (a) a solitary nodule appearing after a long interval is will be removed in most instances, (b) surgery is rarely advocated when there are multiple metastases present at the time of surgery on the primary colorectal cancer or appearing soon after.

These scenarios represent opposite ends of the continuum of favourable to adverse factors for survival after resection of pulmonary metastases. Most patients operated on fall between these extremes and it is evident that if there is a "yes" towards one end of the continuum and "no" towards the other that there must be cross over zone where there is clinical uncertainty. PulMiCC aims to investigate the outcome following pulmonary metastasectomy in patients where there is accepted clinical uncertainty, to provide evidence to guide practice in the future.

It has also been shown previously that trials requiring patients to consider randomisation between treatments that appear very different, as in this instance between surgery or no surgery, can experience recruitment difficulties. This is because potential participants may have acquired a strong preference for one of the treatments over the other and they are not willing to accept the possibility of being allocated to the less non-preferred option alternative.

There can also be problems of bias if one treatment is mentioned to the patient before the option of a trial is introduced; the first mentioned treatment may be perceived to be preferred between doctor and patient. This trial has been designed to overcome these potential difficulties and maximise recruitment as follows.

Colorectal cancer patients presenting with pulmonary metastases will first be consented for registration into the study. This consent is to undergo evaluation according to the trial protocol as part of the work up for consideration by the MDT. Following evaluation, the MDT will consider how they would normally treat each patient according to their standard local practice. Patients eligible for randomisation will be those for whom clinical uncertainty exists as to whether surgery would be of benefit. This trial design was successful in a study of the feasibility of randomising patients in a trial of mesothelioma surgery.

The time taken for patients to undergo the full range of tests for evaluation gives them time to think carefully about the possible treatment options and discuss them with their doctor. In addition to the patient information leaflet, patients will be invited to take home a DVD explaining the trial in detail, which can be watched as often as the patient likes. It is hoped that those who are ultimately identified as eligible for randomisation will have fewer anxieties because of their extended opportunity to consider the trial.

Local site research staff involved in recruiting patients will attend a training session to learn the best method of informing patients about the trial before recruitment commences.

Study Type

Interventional

Enrollment (Actual)

93

Phase

  • Not Applicable

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

      • Zhengzhou, China, 450000
        • Henan Cancer Hospital/The affiliated Cancer Hospital
      • Catania, Italy, 95124
        • Policlinico Hospital
      • Sremska Kamenica, Serbia, 21204
        • Institute for Lung diseases of Vojvodina
      • Basildon, United Kingdom, SS16 5NL
        • Basildon University Hospital
      • Birmingham, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital
      • Bristol, United Kingdom, BS2 8HW
        • Bristol Royal Infirmary
      • Burton upon Trent, United Kingdom, DE13 0RB
        • Queen's Hospital
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
      • Glasgow, United Kingdom, G81 4DY
        • Golden Jubilee National Hospital
      • Leicester, United Kingdom, LE3 9QP
        • Glenfield Hospital
      • Liverpool, United Kingdom, L14 3PE
        • Liverpool Heart & Chest Hospital
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • London, United Kingdom, SW17 0QT
        • St George's Hospital
      • London, United Kingdom, SW3 6NP
        • Royal Brompton Hospital
      • London, United Kingdom, SE1 7EH
        • Guy's and St Thomas' NHS Trust
      • London, United Kingdom, N19 5NF
        • The Whittington Hospital
      • Manchester, United Kingdom, M20 4BX
        • The Christie Nhs Foundation Trust
      • Middlesbrough, United Kingdom, TS4 3BW
        • James Cook University Hospital
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Freeman Hospital
      • Nottingham, United Kingdom, NG5 1PB
        • Nottingham City Hospital
      • Papworth Everard, United Kingdom, CB23 3RE
        • Papworth Hospital NHS Trust
      • Plymouth, United Kingdom, PL6 8DH
        • Derriford Hospital
      • Sheffield, United Kingdom, S5 7AU
        • Sheffield Teaching Hospitals
      • Wolverhampton, United Kingdom, WV10 0QP
        • New Cross Hospital

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

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with primary colorectal cancer who have undergone resection of the primary cancer with intent to cure, local control has been confirmed and no clinical indications of other active colorectal cancer other than the known lung metastases.

Exclusion Criteria:

  • Previous malignancy likely to interfere with protocol treatment or measurement of endpoints, any concurrent illness which could interfere with the treatment protocol or confound survival, unavailable for follow up and assessment according to protocol, psychiatric or mental incapacity that precludes fully informed consent

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
Intervention / Treatment
Experimental: Pulmonary metastasectomy
Pulmonary Metastasectomy
Active Comparator: Active monitoring
Active monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of recruitment
Time Frame: 2 years
We wish to measure the monthly recruitment rate from approximately 11-12 centres over 2 years. This feasibility study aims to determine whether it will be possible to recruit sufficient patients to conduct a larger randomised trial which would be powered to measure survival as the primary outcome.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: 5 years
Overall survival, Relapse free survival, Lung function (measured by FEV1), Patient reported quality of life (STAI, FACT-An-L and EQ-5D questionnaires), Health economic assessment
5 years

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Tom Treasure, MD, MS, FRCS, UCL

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.

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)

December 2, 2010

Primary Completion (Actual)

November 24, 2016

Study Completion (Actual)

February 29, 2020

Study Registration Dates

First Submitted

April 13, 2010

First Submitted That Met QC Criteria

April 16, 2010

First Posted (Estimate)

April 19, 2010

Study Record Updates

Last Update Posted (Estimate)

May 11, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • Reference No: 08/0390
  • CRUK/09/022 (Other Grant/Funding Number: Cancer Research UK)

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.

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