Reduced frequency pembrolizumab immunotherapy: can the frequency of pembrolizumab treatment for non-small cell lung cancer be reduced without reducing its effectiveness?

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-how-often-to-give-pembrolizumab-for-non-small-lung-cancer-refine-lung

Background and study aims
Lung cancer is the most common cause of cancer death. Things have improved with the use of drugs like pembrolizumab, which is often used following a diagnosis of advanced non-small cell lung cancer (NSCLC). Pembrolizumab uses the immune system, the body’s natural defence. The immune system sends cells called T cells to fight infections and diseases. Cancer cells hide in the ‘PD-1/PD-L1 pathway’, allowing them to grow and spread. Pembrolizumab blocks the pathway. This prevents cancer cells from hiding, meaning they can be killed by T cells. The cancer may shrink or disappear as a result.
Treatment is usually every 6 weeks, sometimes with chemotherapy. Treatment can last 2 years, and this may be too much. Research has not shown that length increases benefit, and many people who stop before 2 years continue to benefit from pembrolizumab after it has finished.
There is a possibility that researchers can reduce treatment frequency without effectiveness being reduced. This is the main aim of REFINE-Lung.

Who can participate?
Eligible participants will be about to or already receiving pembrolizumab as first treatment for NSCLC.

What does the study involve?
Participants will be randomly allocated to one of the following with or without chemotherapy until the cancer grows significantly:
- Pembrolizumab 6 weekly – the ‘control’ group, or standard treatment;
- Pembrolizumab 12 weekly.

After 150 participants are recruited, the researchers will see if 12 weekly is similar to 6 weekly, and if so 3 further groups will be opened:
- Pembrolizumab 9 weekly;
- Pembrolizumab 15 weekly;
- Pembrolizumab 18 weekly.

Up to 350 participants will be recruited into each group from up to 45 participating UK hospitals, 1750 in total. Each participant will be followed up for 18 months.

What are the possible benefits and risks of participating?
Benefits:
Similar effectiveness but fewer side effects
Improved quality of life
Fewer visits to and savings by hospitals
Risks:
CT Scans: The risk of causing cancer from one scan is around 1 in 1,000, in a healthy person. The dose from a scan is similar to 9 years of background radiation. Subjects would receive the scans as part of their normal care and the risks are considered low because of their existing condition. The patient may find the CT scanner claustrophobic. A contrast dye may be used which may cause discomfort, bruising, swelling and sometimes an allergic reaction. Severe reactions are very rare.
Blood collection: There is a possibility of redness, swelling and bruising after collection and participants may feel lightheaded or faint. The blood samples collected are not above those that would be performed routinely.
Pembrolizumab: Pembrolizumab is a common treatment for NSCLC. The common side effects are related to the immune system and include itching/rash, diarrhoea, cough, muscle/joint pain, fever, abdominal pain, sickness, headache and tiredness. The research arms reduce the treatment frequency which may reduce the side effects and reduce the burden on patients. Participants may be hesitant about this causing disease progression, hence we have allowed re-escalation to 6-weekly treatment.
Pregnancy: The risks are unknown, however, patients are aware of this having been on this treatment for the previous 6 months. Women who become pregnant will be withdrawn and female and male subjects must agree to take appropriate precautions to avoid pregnancy or fathering a child.
Data Protection: Agreements will be in place prior to the transfer of data externally and pseudo-anonymised will be sent to avoid participant identification.
COVID-19: Patients are included in the at-risk categories but the aim of the study is to reduce the required visits. It is recommended that the vaccine be given as per current guidance for immunotherapy.
Additional visits: The patients will not have to attend hospital more than normal, except for an additional two visits for the screening and end of treatment.

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
January 2022 to May 2027

Who is funding the study?
The National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (UK).

Who is the main contact?
refine-lung@imperial.ac.uk

Study website

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

Imperial College London
University/education

Imperial Clinical Trials Unit – Cancer
Cancer Research UK Convergence Science Centre
Department of Surgery and Cancer
Imperial College London
5th Floor Roderic Hill Building
South Kensington Campus
Prince Consort Road
London
SW7 2AZ
England
United Kingdom

Phone	+44 (0)20 7594 2796
Email	p.badman@imperial.ac.uk
Website	http://www.imperial.ac.uk/
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

ISRCTN70247820 REFINE-Lung protocol v2.0_21Feb22.pdf

ISRCTN70247820 REFINE-Lung PIS Stage 1_V2.0 21Feb22.pdf

ISRCTN70247820_PROTOCOL_V4.0_05Jul22.pdf

ISRCTN70247820_PIS_V2.2_12Jul22.pdf

ISRCTN70247820 REFINE-Lung protocol v5.0_19Oct22.pdf

ISRCTN70247820 REFINE-Lung PIS Stage 2_v3.0_05Oct22.pdf

ISRCTN70247820_PROTOCOL_v6.0_10Mar23.pdf

ISRCTN70247820_ PIS_Stage 2_v3.1_10Mar23.pdf

Editorial Notes

28/08/2024: The study participating centres were updated to add St Johns Hospital, North Devon District Hospital, The Royal Marsden Hospital, Kingston Hospital, Worthing Hospital, Poole Hospital, Victoria Hospital, and Addenbrookes.
04/07/2023: The following changes were made to the study record:
1. Protocol and PIS uploaded.
2. The exclusion criteria and sponsor details were updated.
23/03/2023: The following changes were made to the trial record:
1. Uploaded protocol v5.0 (not peer-reviewed) as an additional file.
2. The participant information sheet v3.0 was uploaded as an additional file.
3. The trial participating centres Freeman Hospital, Milton Keynes University Hospital, Heartlands Hospital were removed and Yeovil District Hospital NHS Foundation Trust, Barts Health NHS Trust, Northampton General Hospital NHS Trust, Calderdale and Huddersfield NHS Foundation Trust.
13/10/2022: The plain English summary was updated with a link to CRUK.
29/09/2022: The following changes were made to the trial record:
1. Uploaded protocol (not peer reviewed) and patient information sheet.
2. Royal Sussex County Hospital, The Royal Bournemouth Hospital, Kettering General Hospital, Milton Keynes University Hospital, and North Middlesex University Hospital were added to the trial participating centres.
21/06/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/06/2022 to 20/06/2022.
2. The ethics approval has been added.
3. The individual participant data (IPD) sharing statement has been added and the IPD sharing summary has been changed from "Data sharing statement to be made available at a later date" to "Available on request".
4. The trial website has been added.
01/04/2022: added CPMS number to Protocol /serial number field.
10/03/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 10/03/2022
21/01/2022: Trial's existence confirmed by NHS HRA.