VIdeo Assisted Thoracoscopic Lobectomy Versus Conventional Open LobEcTomy for Lung Cancer (VIOLET)

September 18, 2020 updated by: University of Bristol

VIdeo Assisted Thoracoscopic Lobectomy Versus Conventional Open LobEcTomy for Lung Cancer, a Multi-centre Randomised Controlled Trial With an Internal Pilot

Lung cancer is the leading cause of cancer death worldwide and survival in the United Kingdom (UK) remains amongst the lowest in Europe. Surgery is the main method of managing early stage disease and is traditionally undertaken via conventional open surgery. However, over the last decade there has been a surge in the number of minimal access resections performed using Video-assisted thoracoscopic surgery (VATS). However, there remains a need for well-designed and conducted randomised controlled trial (RCT) to provide the evidence base for the wide spread uptake and delivery of this surgical approach.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The uptake of surgery for lung cancer in the UK is low and minimal access surgery may be regarded as a more acceptable intervention (compared to open surgery) by patients, referring respiratory physicians and oncologists. However, a large multi-centre RCT is essential to inform patient and clinician decision making and influence surgical practice in the UK.

The VIOLET study will compare the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open surgery for treatment of lung cancer and will test the hypothesis that VATS surgery is superior to open surgery with respect to self-reported physical function five weeks after randomisation (approx. one month after surgery).

Specific objectives are to estimate:

A. The difference between groups in the average self-reported physical function at five weeks.

B. The difference between groups with respect to a range of secondary outcomes including assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pN2 disease and disease free survival) and overall survival.

C. The cost effectiveness of VATs and open surgery.

Study Type

Interventional

Enrollment (Actual)

503

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

  • United Kingdom
      • Birmingham, United Kingdom
        • Heartlands Hospital
      • Bristol, United Kingdom
        • Bristol Royal Infirmary
      • Edinburgh, United Kingdom
        • Royal Infirmary of Edinburgh
      • Hull, United Kingdom
        • Hull and East Yorkshire Hospitals NHS Trust
      • Liverpool, United Kingdom
        • Liverpool Heart and Chest Hospital NHS Foundation Trust
      • London, United Kingdom
        • Royal Brompton Hospital
      • London, United Kingdom
        • Harefield Hospital
      • Middlesbrough, United Kingdom
        • The James Cook University Hospital
      • Oxford, United Kingdom
        • Oxford University Hospitals NHS Foundation Trust

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adults aged ≥16 years of age

  2. Able to give written consent, undergoing either:

    i. Lobectomy or bilobectomy for treatment of known or suspected primary lung cancer beyond lobar orifice* in TNM8 stage cT1-3 (by size criteria, equivalent to TNM7 stage cT1a-2b) or cT3 (by virtue of 2 nodules in the same lobe), N0-1 and M0 or ii. Undergoing frozen section biopsy with the intention to proceed with lobectomy or bilobectomy if primary lung cancer with a peripheral tumour beyond a lobar orifice* in TNM8 stage cT1-3 (by size criteria, equivalent to TNM7 stage cT1a-2b) or cT3 (by virtue of 2 nodules in the same lobe), N0-1 and M0 is confirmed

  3. Disease suitable for both minimal access (VATS) and open surgery

Exclusion Criteria:

  1. Adults lacking capacity to consent
  2. Previous malignancy that influences life expectancy
  3. Patients in whom a pneumonectomy, segmentectomy or non-anatomic resection (e.g. wedge resection) is planned
  4. Patients with a serious concomitant disorder that would compromise patient safety during surgery.
  5. Planned robotic surgery

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VATS lobectomy
VATS lobectomy is undertaken through one to four keyhole incisions without rib spreading. The use of 'rib spreading' is prohibited as this is the key intra-operative manoeuvre which disrupts tissues and causes pain (and is used in open surgery). The procedure is performed with videoscopic visualisation without direct vision. The hilar structures are dissected, stapled and divided. Endoscopic ligation of pulmonary arterial branches may be performed. The fissure is completed and the lobe of lung resected. Lymph node management is the same as described for open surgery. The incisions are closed in layers and may involve muscle, fat and skin layers. This definition of VATS lobectomy is a modification of CALGB 39802.
Procedure: Video Assisted Thoracoscopic Surgery (VATS)
VATS lobectomy is undertaken through one to four keyhole incisions without rib spreading. The use of 'rib spreading' is prohibited as this is the key intra-operative manoeuvre which disrupts tissues and causes pain (and is used in open surgery). The procedure is performed with videoscopic visualisation without direct vision. The hilar structures are dissected, stapled and divided. Endoscopic ligation of pulmonary arterial branches may be performed. The fissure is completed and the lobe of lung resected. Lymph node management is the same as described for open surgery. The incisions are closed in layers and may involve muscle, fat and skin layers. This definition of VATS lobectomy is a modification of CALGB 39802.
Other Names:
  • VATS lobectomy
Active Comparator: Open lobectomy
Conventional open surgery is undertaken through a single incision +/- rib resection and with rib spreading. The operation is performed under direct vision with isolation of the hilar structures (vein, artery and bronchus) which are dissected, ligated and divided in sequence and the lobe of lung resected. The procedures may be undertaken using ligatures, over sewing or with staplers. Lymph node management is undertaken in accordance with the International Association of the Study of Lung Cancer (IASLC) recommendations where a minimal of 6 nodes / stations are removed, of which 3 are from the mediastinum that includes the subcarinal station. The thoracotomy is closed in layers starting from pericostal sutures over the ribs, muscle, fat and skin layers.
Procedure: Open Surgery
Conventional open surgery is undertaken through a single incision +/- rib resection and with rib spreading. The operation is performed under direct vision with isolation of the hilar structures (vein, artery and bronchus) which are dissected, ligated and divided in sequence and the lobe of lung resected. The procedures may be undertaken using ligatures, over sewing or with staplers. Lymph node management is undertaken in accordance with the International Association of the Study of Lung Cancer (IASLC) recommendations where a minimal of 6 nodes / stations are removed, of which 3 are from the mediastinum that includes the subcarinal station. The thoracotomy is closed in layers starting from pericostal sutures over the ribs, muscle, fat and skin layers.
Other Names:
  • Open lobectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Self-reported physical function using HRQoL questionnaire QLQ-C30
Time Frame: 5 weeks post randomisation
Physical functioning scale, ranges between 0 and 100. High score indicates high level of physical functioning.
5 weeks post randomisation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time from surgery to hospital discharge, assessed up to 12 months
Time Frame: Time from surgery to hospital discharge, assessed up to 12 months
Time from surgery to hospital discharge, assessed up to 12 months
Adverse health events to 1 year
Time Frame: Adverse health events to 1 year
Adverse health events to 1 year
Proportion of patients taking up adjuvant treatment, assessed up to 12 months
Time Frame: Proportion and time to uptake of adjuvant treatment, assessed up to 12 months
Proportion and time to uptake of adjuvant treatment, assessed up to 12 months
Time to uptake of adjuvant treatment, assessed up to 12 months
Time Frame: Proportion and time to uptake of adjuvant treatment, assessed up to 12 months
Proportion and time to uptake of adjuvant treatment, assessed up to 12 months
Proportion of patients upstaged to pN2 disease after surgical procedure, assessed up to 3 months post surgery
Time Frame: Proportion of patients upstaged to pN2 disease after surgical procedure, assessed up to 3 months post-surgery
Proportion of patients upstaged to pN2 disease after surgical procedure, assessed up to 3 months post-surgery
Overall and disease-free survival to 1-year
Time Frame: 1 year
1 year
Proportion of patients who undergo complete resection during the procedure, , assessed up to 12 months
Time Frame: Proportion of patients who undergo complete resection during the procedure, assessed up to 12 months
Proportion of patients who undergo complete resection during the procedure, assessed up to 12 months
Proportion of patients who experience prolonged incision pain (defined as the need of analgesia > 5 weeks post-randomisation)
Time Frame: Up to 1 year
Up to 1 year
Disease-specific HRQoL - EORTC QLQ-C30 to 1-year
Time Frame: Measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation

3 types of scales. Functioning scales which include physical functioning, role functioning, emotional function, cognitive functioning and social functioning. Symptom scales which include fatigue, nausea and vomiting, pain, dysponea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties.

An overall global health status/QoL All scales range between 0 and 100. For functioning scales, a high score indicates a high level of functioning. Similarly, a high global health status/QoL score indicates a high quality of life. For symptom scales, a high score indicates a high level of symptoms.
Measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation
Disease-specific HRQoL - EORTC QLQ-LC13 to 1-year
Time Frame: Measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation

Symptoms scales which include Dyspnoea, Couging, Haemoptysis, Sore mouth, Dysphagia, Peripheral neuropathy, Alopecia, Pain in chest, Pain in arm or shoulder, Pain in other parts, and Pain medication. For these scales, a high score indicates a high level of symptoms, as with the QLQ-C30.

Scales range between 0 and 100.
Measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation
Generic HRQoL - EORTC EQ5D to 1-year
Time Frame: Measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation

Subscales: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. These range from 1-5.

subscales mobility, self-care, usual activities, pain/discomfort, anxiety/depression are combined to calculate an overall index score which ranges from -0.59 to 1.

A higher score indicates better quality of life
Measured at 2 week, 5 weeks, 3 months, 6 months and 1-year post randomisation
Resource use
Time Frame: Up to 1 year
Resource use to 1-year (measured for the duration of post-operative hospital stay until discharge, and at 5 weeks, 3 months, 6 months and 1-year post randomisation)
Up to 1 year

Collaborators and Investigators

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

Sponsor

University of Bristol

Collaborators

University of Oxford
Royal Brompton & Harefield NHS Foundation Trust

Investigators

  • Principal Investigator: Eric Lim, Royal Brompton & Harefield NHS Foundation Trust
  • Study Director: Chris Rogers, University of Bristol

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.

General Publications

Helpful Links

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

July 1, 2015

Primary Completion (Actual)

March 1, 2019

Study Completion (Actual)

March 1, 2020

Study Registration Dates

First Submitted

January 26, 2018

First Submitted That Met QC Criteria

April 27, 2018

First Posted (Actual)

May 11, 2018

Study Record Updates

Last Update Posted (Actual)

September 22, 2020

Last Update Submitted That Met QC Criteria

September 18, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORCA58877

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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