A Randomised Open-label Phase III Trial of REduced Frequency Pembrolizumab immuNothErapy for First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
REFINE-Lung
2 other identifiers
interventional
1,750
1 country
37
Brief Summary
REFINE-lung will test whether reduced pembrolizumab dose frequency after 6 months of standard treatment is safe and effective. Patients treated with 1st line pembrolizumab who are progression free and otherwise planning to continue therapy at 6 months will be initially randomised to control 6 weekly versus interventional 12 weekly therapy. If an interim analysis shows that the 12 weekly treatment is no less effective, subsequent patients will also be randomised to 9, 15 and 18 weekly treatment frequency arms. Patients who progress on a reduced frequency arm will be offered re-escalation to standard 6 weekly therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2022
Longer than P75 for phase_3
37 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 5, 2021
CompletedFirst Posted
Study publicly available on registry
October 20, 2021
CompletedStudy Start
First participant enrolled
June 23, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2027
March 7, 2024
March 1, 2024
4.9 years
October 5, 2021
March 6, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Overall survival at 2 years
Survival at 2 years, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination
18 months from randomisation
Secondary Outcomes (5)
Overall survival from study entry
2 years
Progression free survival
2 years
Overall response rate
2 years
Duration of response
2 years
Incidence of adverse events
2 years
Study Arms (5)
6 weekly
ACTIVE COMPARATOR6 weekly pembrolizumab, 400mg intravenous
9 weekly
EXPERIMENTAL9 weekly pembrolizumab, 400mg intravenous
12 weekly
EXPERIMENTAL12 weekly pembrolizumab, 400mg intravenous
15 weekly
EXPERIMENTAL15 weekly pembrolizumab, 400mg intravenous
18 weekly
EXPERIMENTAL18 weekly pembrolizumab, 400mg intravenous
Interventions
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies
Eligibility Criteria
You may qualify if:
- Written informed consent prior to initiation of any study procedures and willingness and ability to comply with the study schedule
- Any patient ≥18yrs who has received 6 months of pembrolizumab treatment with or without chemotherapy for advanced Non small cell lung cancer who is planned to continue immunotherapy treatment because of continued benefit.
You may not qualify if:
- Disease progression or not tolerating treatment at 6 months into therapy
- Clinician does not intend to continue immunotherapy
- Any patient with a synchronous primary cancer. This includes any new cancer diagnoses or relapse of previously treated cancer since starting pembrolizumab treatment.
- Any patient currently receiving an investigational agent and/or using an investigational device or has participated in a study of an investigational agent and/or used an investigational device within 28 days of randomisation.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Imperial College Londonlead
- National Institute for Health Research, United Kingdomcollaborator
- Medical Research Councilcollaborator
- University College, Londoncollaborator
Study Sites (37)
Royal Bournemouth Hospital
Bournemouth, United Kingdom
Royal Sussex County Hospital
Brighton, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, United Kingdom
Queen's Hospital
Burton-on-Trent, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom
East Kent Hospitals University NHS Foundation Trust
Canterbury, United Kingdom
Velindre Cancer Centre
Cardiff, United Kingdom
Colchester Hospital
Colchester, United Kingdom
Royal Derby Hospital
Derby, United Kingdom
NHS Lothian
Edinburgh, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
New Victoria Hospital
Glasgow, United Kingdom
Royal Surrey NHS Foundation Trust
Guildford, United Kingdom
Calderdale & Huddersfield NHS Foundation Trust
Huddersfield, United Kingdom
Ipswich Hospital
Ipswich, United Kingdom
Kettering General Hospital
Kettering, United Kingdom
NHS Fife
Kirkcaldy, United Kingdom
Forth Valley Royal Hospital
Larbert, United Kingdom
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool, United Kingdom
Guys Hospital
London, United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom
North Middlesex University Hospital NHS Trust
London, United Kingdom
St Bartholomew's Hospital
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Northampton General Hospital NHS Trust
Northampton, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Peterborough City Hospital
Peterborough, United Kingdom
Poole Hospital
Poole, United Kingdom
Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
Romford, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT, United Kingdom
Royal Cornwall Hospital
Truro, United Kingdom
Worthing Hospital
Worthing, United Kingdom
Yeovil Hospital
Yeovil, United Kingdom
Related Publications (1)
Ghorani E, Quartagno M, Blackhall F, Gilbert DC, O'Brien M, Ottensmeier C, Pizzo E, Spicer J, Williams A, Badman P, Parmar MKB, Seckl MJ; REFINE-Lung Investigators. REFINE-Lung implements a novel multi-arm randomised trial design to address possible immunotherapy overtreatment. Lancet Oncol. 2023 May;24(5):e219-e227. doi: 10.1016/S1470-2045(23)00095-5.
PMID: 37142383DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Seckl
Imperial College London
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 5, 2021
First Posted
October 20, 2021
Study Start
June 23, 2022
Primary Completion (Estimated)
May 31, 2027
Study Completion (Estimated)
May 31, 2027
Last Updated
March 7, 2024
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will not share