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)
Primary Purpose
Lung Cancer, Nonsmall Cell
Status
Recruiting
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Pembrolizumab 25 MG/ML [Keytruda]
Sponsored by
About this trial
This is an interventional treatment trial for Lung Cancer, Nonsmall Cell
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Disease progression or not tolerating treatment at 6 months into therapy
- Clinician does not intend to continue immunotherapy
Sites / Locations
- Royal Bournemouth HospitalRecruiting
- Bristol Haematology and Oncology CentreRecruiting
- Queen's HospitalRecruiting
- East Kent Hospitals University NHS Foundation TrustRecruiting
- Velindre Cancer CentreRecruiting
- Colchester HospitalRecruiting
- Royal Derby HospitalRecruiting
- NHS LothianRecruiting
- Royal Devon and Exeter HospitalRecruiting
- Beatson West of Scotland Cancer CentreRecruiting
- New Victoria HospitalRecruiting
- Ipswich HospitalRecruiting
- Kettering General HospitalRecruiting
- Forth Valley Royal HospitalRecruiting
- Leeds Teaching Hospitals NHS TrustRecruiting
- Leicester Royal InfirmaryRecruiting
- Guys HospitalRecruiting
- Imperial College Healthcare NHS TrustRecruiting
- The Christie NHS Foundation TrustRecruiting
- Nottingham University Hospitals NHS TrustRecruiting
- Peterborough City HospitalRecruiting
- Poole HospitalRecruiting
- Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS TrustRecruiting
- The Royal Marsden NHS Foundation TrustRecruiting
- Royal Cornwall HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
6 weekly
9 weekly
12 weekly
15 weekly
18 weekly
Arm Description
6 weekly pembrolizumab, 400mg intravenous
9 weekly pembrolizumab, 400mg intravenous
12 weekly pembrolizumab, 400mg intravenous
15 weekly pembrolizumab, 400mg intravenous
18 weekly pembrolizumab, 400mg intravenous
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Overall survival from study entry
Survival, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination
Progression free survival
Progression free survival as assessed by RECIST v1.1, defined as time from study entry to first evidence of disease progression or death due to any cause
Overall response rate
Overall response rate (ORR) as assessed by RECIST v1.1, defined as complete response (CR) or partial response (PR)
Duration of response
Duration of response (DoR) as assessed by RECIST v1.1, defined as time from study entry to change in response from CR or PR to stable disease (SD) or progressive disease (PD)
Incidence of adverse events
Safety and tolerability as assessed by adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Full Information
NCT ID
NCT05085028
First Posted
October 5, 2021
Last Updated
July 4, 2023
Sponsor
Imperial College London
Collaborators
National Institute for Health Research, United Kingdom, Medical Research Council, University College, London
1. Study Identification
Unique Protocol Identification Number
NCT05085028
Brief Title
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)
Acronym
REFINE-Lung
Official Title
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) Utilising a Novel Multi-arm Frequency-response Optimisation Design
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 23, 2022 (Actual)
Primary Completion Date
May 31, 2027 (Anticipated)
Study Completion Date
May 31, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
National Institute for Health Research, United Kingdom, Medical Research Council, University College, London
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
Immunotherapy with pembrolizumab targeting the T cell inhibitory PD-1 receptor has significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). Approximately 3600 new patients are treated in the 1st line setting per year in England alone and up to 25% remain on 6 weekly pembrolizumab for 2 years. However, pharmacological and clinical trial data suggest current frequent dosing for 2 years result in overtreatment. Indeed, pembrolizumab remains bound to its target receptor for up to 100 days following a single dose and studies in multiple tumour types have found no relationship between dose and patient outcome. Moreover, anti-PD1 treated patients who respond but discontinue therapy either as planned after 2 years, or earlier because of toxicity, can either remain in remission and/or be sensitive to re-challenge with pembrolizumab.
REFINE-lung will test whether reduced pembrolizumab dose frequency (9, 12, 15, 18 weeks) after 6 months of standard treatment is safe and effective.
This UK study represents a unique opportunity to determine whether pembrolizumab dose frequency can be safely reduced in NSCLC, resulting in significant cost benefits to the NHS and globally, in addition to enhanced patient QoL associated with fewer hospital attendances and reduced toxicity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Nonsmall Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1750 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
6 weekly
Arm Type
Active Comparator
Arm Description
6 weekly pembrolizumab, 400mg intravenous
Arm Title
9 weekly
Arm Type
Experimental
Arm Description
9 weekly pembrolizumab, 400mg intravenous
Arm Title
12 weekly
Arm Type
Experimental
Arm Description
12 weekly pembrolizumab, 400mg intravenous
Arm Title
15 weekly
Arm Type
Experimental
Arm Description
15 weekly pembrolizumab, 400mg intravenous
Arm Title
18 weekly
Arm Type
Experimental
Arm Description
18 weekly pembrolizumab, 400mg intravenous
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab 25 MG/ML [Keytruda]
Intervention Description
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies
Primary Outcome Measure Information:
Title
Overall survival at 2 years
Description
Survival at 2 years, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination
Time Frame
18 months from randomisation
Secondary Outcome Measure Information:
Title
Overall survival from study entry
Description
Survival, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination
Time Frame
2 years
Title
Progression free survival
Description
Progression free survival as assessed by RECIST v1.1, defined as time from study entry to first evidence of disease progression or death due to any cause
Time Frame
2 years
Title
Overall response rate
Description
Overall response rate (ORR) as assessed by RECIST v1.1, defined as complete response (CR) or partial response (PR)
Time Frame
2 years
Title
Duration of response
Description
Duration of response (DoR) as assessed by RECIST v1.1, defined as time from study entry to change in response from CR or PR to stable disease (SD) or progressive disease (PD)
Time Frame
2 years
Title
Incidence of adverse events
Description
Safety and tolerability as assessed by adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alex Williams
Phone
020 7594 2180
Email
a.williams@imperial.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Philip Badman
Email
philip.badman@imperial.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Seckl
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tom Geldart
Email
Tom.geldart@uhd.nhs.uk
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adam Dangoor
Email
adam.dangoor@uhbw.nhs.uk
Facility Name
Queen's Hospital
City
Burton Upon Trent
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manjusha Keni
Email
manjusha.keni@nhs.net
Facility Name
East Kent Hospitals University NHS Foundation Trust
City
Canterbury
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathilda Cominos
Email
mathilda.cominos@nhs.net
Facility Name
Velindre Cancer Centre
City
Cardiff
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Shaw
Email
Paul.P.Shaw@wales.nhs.uk
Facility Name
Colchester Hospital
City
Colchester
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dakshinamoorthy Muthukumar
Email
Muthu.Kumar@esneft.nhs.uk
Facility Name
Royal Derby Hospital
City
Derby
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manjusha Keni
Email
manjusha.keni@nhs.net
Facility Name
NHS Lothian
City
Edinburgh
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Colin Barrie
Email
Colin.Barrie@nhslothian.scot.nhs.uk
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Petru Belitei
Email
p.belitei@nhs.net
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ishtiaq Zubairi
Email
Ishtiaq.Zubairi@ggc.scot.nhs.uk
Facility Name
New Victoria Hospital
City
Glasgow
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicola Steele
Email
Nicola.Steele@ggc.scot.nhs.uk
Facility Name
Ipswich Hospital
City
Ipswich
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kent Yip
Email
KENT.YIP@ESNEFT.NHS.UK
Facility Name
Kettering General Hospital
City
Kettering
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georgios Tsaknis
Email
georgios.tsaknis@nhs.net
Facility Name
Forth Valley Royal Hospital
City
Larbert
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicola Steele
Email
Nicola.Steele@ggc.scot.nhs.uk
Facility Name
Leeds Teaching Hospitals NHS Trust
City
Leeds
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pooja Jain
Email
pjain@nhs.net
Facility Name
Leicester Royal Infirmary
City
Leicester
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samreen Ahmed
Email
samreen.ahmed@uhl-tr.nhs.uk
Facility Name
Guys Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Spicer
Email
james.spicer@kcl.ac.uk
Facility Name
Imperial College Healthcare NHS Trust
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joanne Evans
Email
joanne.evans10@nhs.net
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabio Gomes
Email
fabio.gomes2@nhs.net
Email
the-christie.LungResearchTeam@nhs.net
Facility Name
Nottingham University Hospitals NHS Trust
City
Nottingham
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jason Adhikaree
Email
Jason.Adhikaree2@nuh.nhs.uk
Facility Name
Peterborough City Hospital
City
Peterborough
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Treece
Email
streece@nhs.net
Facility Name
Poole Hospital
City
Poole
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tom Geldart
Email
Tom.geldart@uhd.nhs.uk
Facility Name
Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
City
Romford
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathryn Tarver
Email
k.tarver@nhs.net
Facility Name
The Royal Marsden NHS Foundation Trust
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mary O'Brien
Email
Mary.OBrien@rmh.nhs.uk
Facility Name
Royal Cornwall Hospital
City
Truro
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grant Stewart
Email
grantstewart1@nhs.net
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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)
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