Oral vinorelbine as second-line therapy for patients with malignant pleural mesothelioma

ISRCTN	ISRCTN44518069
DOI	https://doi.org/10.1186/ISRCTN44518069
EudraCT/CTIS number	2014-001992-30
ClinicalTrials.gov number	NCT02139904
Secondary identifying numbers	32185

Submission date: 16/01/2017
Registration date: 23/01/2017
Last edited: 05/10/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-vinorelbine-for-people-with-advanced-pleural-mesothelioma-vim

Study website

Contact information

Mrs Georgina Gardner
Public

Wales Cancer Trials Unit
Centre for Trials Research
Cardiff University
6th Floor, Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom

Phone	+44 29 2068 7950
Email	VIM@Cardiff.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment, Drug
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	ISRCTN44518069_PIS_15Oct14_V3.pdf
Scientific title	A randomised controlled phase II trial of oral vinorelbine as second line therapy for patients with malignant pleural mesothelioma
Study acronym	VIM
Study objectives	The aim of this study it to establish whether treatment with vinorelbine in patients with malignant pleural mesothelioma (MPM) actually makes them live longer.
Ethics approval(s)	Wales REC 3, 22/10/2014, ref: 14/WA/1054
Health condition(s) or problem(s) studied	Specialty: Cancer, Primary sub-specialty: Lung Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs
Intervention	Participants will be randomised (1:2) to receive either active symptom control (ASC) or ASC with vinorelbine. Participant randomisation will be performed centrally by the WCTU. Group A: Participants receive active supportive care only for the duration of the study. Active supportive care is defined as the treatments and procedures used locally to control the symptoms of mesothelioma. Examples of symptoms and possible treatments are listed below, but this list is not exhaustive and any supportive treatment may be classed as ASC. Breathlessness: Chest drain, relaxation, posture advice, medication, anti-anxiety medication, oxygen Pain Painkillers, relaxation, massage, referral to specialist pain clinics Night sweats: Management advice, medication Loss of appetite: High protein powders/high calorie drinks, steroids, nutritional advice, supplements Tiredness: Sleep advice, gentle exercise Anaemia: Blood transfusion Depression: Counselling, anti-depressants Other: Acupuncture, massage, aromatherapy and relaxation technique Group B: Patients will be treated with ASC as above, plus vinorelbine. Vinorelbine (Navelbine) should be administered at a dose of 60mg/m2 orally weekly for the first cycle (days 1, 8 and 15) on a 3-weekly cycle. Subsequent doses should be increased to 80mg/m2 (day 22) if there has been no haematological toxicity. Patients remain on ASC or treatment until disease progression (or unacceptable toxicity or patient withdrawal). There will be a follow-up assessment at disease progression/End of treatment (Arm B only) and follow-up assessment 30 days after disease progression/End of treatment (Arm B only). Trial follow-up will continue for 18 months after the last participant is randomised.
Intervention type	Other
Primary outcome measure	Overall survival will be measured as time from randomisation to death (from any cause).
Secondary outcome measures	1. Progression free survival is assessed by modified RECIST using baseline CT scan results compared against further CT scans on Day 1 of each cycle of treatment 2. Safety and tolerability and feasibility of use will be assessed during and after treatment by collection of toxicities according to NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 at every clinic visit and reporting of SAEs in real-time 3. Objective response rate as assessed by modified RECIST using baseline CT scan results compared against further CT scans on Day 1 of each cycle of treatment
Overall study start date	11/09/2013
Completion date	01/09/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 200; UK Sample Size: 200
Total final enrolment	154
Key inclusion criteria	1. Confirmed histological diagnosis of malignant pleural mesothelioma. The same block or 10 unstained slides should be available for translational research 2. Prior treatment with first-line standard platinum doublet based chemotherapy. Re-challenge with first line chemotherapy is allowed. 3. Evidence of disease progression according to CT scan on Modified RECIST 4. Life expectancy ≥ 3 months 5. ECOG performance status 0-1 6. Men or women aged 18 years or over 7. Willing to consent to provide blood and tissue for translational research 8. Disease which is measurable using modified RECIST 9. Adequate organ function, including the following: Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, WBC ≥3 x 109/L, haemoglobin ≥ 100g/L, platelets ≥ 100 x 109/L; adequate liver function: Bilirubin < 1.5 x ULN AST/ALT < 1.5- 2.5 x ULN. 10. Patients with reproductive potential (male or female), who are sexually active during the duration of the trial or the drug washout period, should be prepared to use two effective forms of contraception throughout their participation in the trial and for at least three months after the last dose of vinorelbine. Effective forms of contraception would include condom with spermicide, along with one of the following: oral contraceptive or hormonal therapy (e.g. hormone implants); placement of an inter-uterine device; vasectomy with assurance of post- vasectomy confirmation of azoospermia; tubal occlusion. Accepted hormonal methods include: Etonogestrel implants; normal and low dose combined oral pills; orelgestromin/ethinyl estradiol transdermal system; or desogestrel. 11. Patients must provide informed consent before any study specific procedures
Key exclusion criteria	1. Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission or patients with a diagnosis of basal cell carcinoma of the skin 2. Have received treatment with an agent that has no marketing authorisation, within 30 days of study entry 3. Are pregnant or breastfeeding. If a participant becomes pregnant during the trial, and is randomised to the treatment arm, vinorelbine must be discontinued and the participant followed up until birth or termination of pregnancy. Breastfeeding must be avoided as it is unknown whether vinorelbine is excreted in human milk. 4. Uncontrolled CNS disease 5. Known contraindication or hypersensitivity to vinorelbine or other vinca alkaloids or to any of the constituents 6. Any disease significantly affecting absorption 7. Previous significant surgical resection of stomach or small bowel 8. Yellow fever vaccine within 30 days of consent 9. Previous vinca alkaloid chemotherapy 10. Palliative radiotherapy within the RECIST area in the 4 weeks prior to baseline CT chest up until randomisation. 11. Patients that are unable to swallow
Date of first enrolment	01/03/2016
Date of final enrolment	31/10/2018

Locations

Countries of recruitment

England
Scotland
United Kingdom
Wales

Study participating centres

Leicester Royal Infirmary

Infirmary Square
Leicester
LE1 5WW
United Kingdom

Velindre NHS Trust

Velindre Road
Whitchurch
Cardiff
CF14 2TL
United Kingdom

Churchill Hospital

Old Road
Headington
Oxford
OX3 7LE
United Kingdom

Aberdeen Royal Infirmary

Foresterhill
Aberdeen
AB25 2ZN
United Kingdom

Sponsor information

University of Leicester
Hospital/treatment centre

Research Governance Office
Fielding Johnson Building
Leicester
LE1 7RH
England
United Kingdom

Phone	+44 116 373 6410/223 1660
Email	uolsponsor@leicester.ac.uk
"ROR"	https://ror.org/04h699437

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	30/09/2020
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Planned publication in a high-impact peer reviewed journal.
IPD sharing plan	The current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	version V3	15/10/2014		No	Yes
Plain English results			06/04/2022	No	Yes
HRA research summary			28/06/2023	No	No

Additional files

ISRCTN44518069_PIS_15Oct14_V3.pdf: Uploaded 23/010/2017

Editorial Notes

06/04/2022: The following changes have been made:
1. The Cancer Research UK lay results summary has been added.
2. The total final enrolment number has been added.
04/07/2019: ClinicalTrials.gov number added.
13/07/2018: The recruitment end date was changed from 01/03/2018 to 31/10/2018
24/10/2017: The registration of this study was requested through the NIHR Portfolio. The trialist confirmed the recruitment start and end dates.
10/04/2017: Link to Cancer Help UK lay summary added to plain English Summary field