CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma (CONFIRM): A Phase III Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy of Nivolumab in Relapsed Mesothelioma

Brief Summary
The UK has the highest incidence of mesothelioma. The incidence has risen by 497% since the late 1970’s and is increasing worldwide due to continued mining and use of asbestos. For patients with mesothelioma who have relapsed after taking pemetrexed and cisplatin, there is currently no standard treatment, making this an urgent unmet need. Recent trials in this area have not found an effective treatment that improves overall survival.

Following a debate in the House of Lords, a national survey assessing the research priorities in mesothelioma found that ‘exploiting the potential of immunotherapy’ was a top priority. This trial was designed in response to that survey. It uses the immunotherapy agent nivolumab which blocks programmed cell death 1 (PD-1) receptor on activated T-cells (a type of white blood cell forming part of the immune system). Early research has found a dependency of mesothelioma on the PD-1 checkpoint. By attaching to PD-1, nivolumab blocks its action (checkpoint inhibition), preventing it from turning off the T-cell, and therefore allowing the immune system to work. PD-1 checkpoint inhibition has revolutionised the treatment of melanoma and it is hoped to be as effective in mesothelioma.

This trial is a randomised, double blind placebo controlled trial of patients with mesothelioma who are third relapse following a platinum based chemotherapy treatment. Patients will be randomised in a 2:1 ratio (nivolumab: placebo).

336 patients will be recruited from 25 UK centres over a four-year period with the last patient having a minimum of 6 months follow up. All patients will be on treatment for 12 months unless they progress or withdrawal prior to this. Clinic visits will occur every 12 weeks, mirroring standard care. Data following progression will be obtained from the NHS Information Centre

Study Type

Study Phase
Phase 3

Study Design
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Drug: Nivolumab

Nivolumab at a dose of 240mg as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle
Other Name: Opdivo

• Other: Placebo

Matched placebo consisting of sterile 0.9% sodium chloride as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle

Study Arms
Experimental: Nivolumab

Nivolumab 240mg flat dose Q2W over 30 minutes IV until disease progression, to a maximum of 12 months
Intervention: Drug: Nivolumab

• Placebo Comparator: Placebo

Sterile 0.9% sodium chloride Q2W over 30 minutes IV until disease progression, to a maximum of 12 months
Intervention: Other: Placebo

University of Southampton

• University of Leicester
• University of Sheffield
• Queen Mary University of London
• Queen’s University, Belfast
• Velindre NHS Trust
• Beatson West of Scotland Cancer Centre

Principal Investigators
Principal investigator:     Dean Fennell     University of Leicester
Principal investigator:     Gareth Griffiths     Southampton Clinical Trials Unit, University of Southampton

Recruitment start: 28/03/2017
Recruitment end: 01/07/2021

Emma Kirkpatrick     023 8120 3785
Kelly Cozens     023 8120 8834