A trial to assess whether nivolumab improves survival in relapsed mesothelioma more than placebo

ISRCTN	ISRCTN79814141
DOI	https://doi.org/10.1186/ISRCTN79814141
EudraCT/CTIS number	2016-003111-35
ClinicalTrials.gov number	NCT03063450
Secondary identifying numbers	32290

Submission date: 27/02/2017
Registration date: 02/03/2017
Last edited: 29/11/2024

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-nivolumab-for-mesothelioma-confirm#undefined

Contact information

Mrs Kelly Cozens
Public

Southampton Clinical Trials Unit
MP131
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Dr Kayleigh Hill
Scientific

Southampton Clinical Trials Unit
MP131
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Study information

Study design	Randomised; Interventional; Design type: Treatment, Drug, Immunotherapy
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	No participant information sheet available
Scientific title	CheckpOiNt blockade For Inhibition of Relapsed Mesothelioma (CONFIRM): A Phase III Trial to Evaluate the Efficacy of Nivolumab in Relapsed Mesothelioma
Study acronym	CONFIRM
Study objectives	The aim of this study is to compare overall survival of nivolumab with placebo in patients with relapsed mesothelioma.
Ethics approval(s)	West Midlands - Edgbaston Research Ethics Committee, 06/12/2016, ref: 16/WM/0472
Health condition(s) or problem(s) studied	Mesothelioma
Intervention	Patients will be randomised 2:1 to nivolumab or placebo, with twice as many people getting nivolumab as placebo. Randomisation will be stratified by site and epithelioid vs. non-epithelioid. Active treatment arm: Patients will be treated with nivolumab at a dose of 240mg, every two weeks, infused over 30 minutes until disease progression, to a maximum of 12 months. Placebo control arm: Patients will receive a placebo consisting of sterile 0.9% sodium chloride, every two weeks, infused over 30 minutes until disease progression, to a maximum of 12 months. All patients will be followed up for a minimum 6 months and maximum of 5 years.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Nivolumab
Primary outcome measure	Overall survival will be calculated as time from randomisation until date of death
Secondary outcome measures	1. Progression free survival is calculated as time from randomisation to disease progression by RECIST 1.1 or modified RECIST using CT scans at baseline compared to further CT scans after cycles 3 and 6 (each cycle is 14 days) 2. Overall response rate is measured by RECIST 1.1 or modified RECIST using CT scans at baseline compared to further CT scans after cycles 3 and 6 (each cycle is 14 days) 3. Quality of life is measured using EQ-5D-5L at baseline, after cycles 3 and 6 (each cycle is 14 days) and 1, 6 and 12 months post progression/treatment discontinuation 4. Toxicity is measured using CTCAE V4.03 at baseline, after each treatment cycle (each cycle is 14 days) and each follow up visit 5. Cost effectiveness is measured using a health resource use questionnaire at baseline, after cycles 3 and 6 (each cycle is 14 days) and 1, 6 and 12 months post progression/treatment discontinuation
Overall study start date	01/10/2016
Completion date	30/09/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 336; UK Sample Size: 336
Total final enrolment	332
Key inclusion criteria	1. Histological confirmation of mesothelioma 2. Prior treatment with at least two lines of platinum based chemotherapy 3. ECOG Performance Status 0-1 4. Evidence of disease progression (which is radiologically assessable through RECIST) on CT scan within 28 days of trial treatment 5. Age 18 and above 6. Screening laboratory values within protocol specified ranges 7. Willing to use adequate contraception methods where applicable 8. Willing to provide blood and tissue samples relating to mesothelioma 9. Expected survival of at least 12 weeks
Key exclusion criteria	1. Untreated, symptomatic CNS metastases 2. Carcinomatous meningitis 3. Active, known or suspected auto-immune disease 4. Those requiring systemic treatment with corticosteroids or immunosuppressive medications within 14 days of planned first dose 5. Other active malignancy requiring treatment 6. Serious or uncontrolled medical disorder or active infection which would impact on the trial or affect their involvement 7. Prior treatment with anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody 8. History of testing positive for HIV or AIDS or a positive test for Hepatitis indicating acute or chronic infection 9. History of allergy or sensitivity to monoclonal antibodies 10. Women who are pregnant or breastfeeding
Date of first enrolment	27/03/2017
Date of final enrolment	27/03/2020

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Southampton Clinical Trials Unit

MP131
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor information

University of Southampton
University/education

Research & Innovation Services
University Road
Southampton
SO17 1BJ
England
United Kingdom

Phone	+44 23 8059 8673
Email	rgoinfo@soton.ac.uk
"ROR"	https://ror.org/01ryk1543

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	30/09/2023
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	The results of the trial will be published in a high-impact peer reviewed scientific journal around six months after overall trial end date.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available for sharing via controlled access by authorised Southampton CTU (SCTU) staff (as delegated to SCTU by the trial sponsor) and anonymised IPD within the clinical trial dataset will be available for sharing via open access after the trial is published.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article		18/04/2018	05/10/2022	Yes	No
HRA research summary			28/06/2023	No	No
Statistical Analysis Plan	version 3	01/08/2022	11/10/2023	No	No
Results article		14/10/2021	22/10/2024	Yes	No

Additional files

ISRCTN79814141 CONFIRM SAP v3 1Aug2022.pdf

Editorial Notes

29/11/2024: A scientific contact was added.
22/10/2024: Publication reference added.
11/10/2023: The statistical analysis plan was uploaded as an additional file.
05/10/2022: Publication reference added.
14/09/2022: The following changes have been made:
1. The overall trial end date was changed from 30/09/2021 to 30/09/2022.
2. The intention to publish date was changed from 30/09/2022 to 30/09/2023.
04/05/2020: The following changes have been made:
1. The recruitment end date has been changed from 23/03/2021 to 27/03/2020.
2. The final enrolment number has been added.
16/01/2020: The ClinicalTrials.gov number has been added.
28/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Lung Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs" to "Mesothelioma" following a request from the NIHR.
05/04/2017: Cancer Help UK lay summary link added to plain English summary field