VIdeo Assisted Thoracoscopic Lobectomy Versus Conventional Open LobEcTomy for Lung Cancer

Lung Neoplasms Clinical Trial

— VIOLET  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03521375
• Other study ID #: ORCA58877
• Status: Completed
• Phase: N/A
• Start date: July 2015
• Est. completion date: March 2020

Study information

• Verified date: September 2020
• Source: University of Bristol
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 503
• Est. completion date: March 2020
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms

Intervention

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.
• 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.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
University of Bristol	Royal Brompton & Harefield NHS Foundation Trust, University of Oxford

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Lim E, Batchelor T, Shackcloth M, Dunning J, McGonigle N, Brush T, Dabner L, Harris R, Mckeon HE, Paramasivan S, Elliott D, Stokes EA, Wordsworth S, Blazeby J, Rogers CA; VIOLET Trialists. Study protocol for VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a UK multicentre randomised controlled trial with an internal pilot (the VIOLET study). BMJ Open. 2019 Oct 14;9(10):e029507. doi: 10.1136/bmjopen-2019-029507. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Self-reported physical function using HRQoL questionnaire QLQ-C30	Physical functioning scale, ranges between 0 and 100. High score indicates high level of physical functioning.	5 weeks post randomisation
Secondary	Time from surgery to hospital discharge, assessed up to 12 months		Time from surgery to hospital discharge, assessed up to 12 months
Secondary	Adverse health events to 1 year		Adverse health events to 1 year
Secondary	Proportion of patients taking up adjuvant treatment, assessed up to 12 months		Proportion and time to uptake of adjuvant treatment, assessed up to 12 months
Secondary	Time to uptake of adjuvant treatment, assessed up to 12 months		Proportion and time to uptake of adjuvant treatment, assessed up to 12 months
Secondary	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
Secondary	Overall and disease-free survival to 1-year		1 year
Secondary	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
Secondary	Proportion of patients who experience prolonged incision pain (defined as the need of analgesia > 5 weeks post-randomisation)		Up to 1 year
Secondary	Disease-specific HRQoL - EORTC QLQ-C30 to 1-year	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
Secondary	Disease-specific HRQoL - EORTC QLQ-LC13 to 1-year	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
Secondary	Generic HRQoL - EORTC EQ5D to 1-year	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
Secondary	Resource use	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

External Links

•   Protocol paper publication