NCT03063450

CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 332 (actual)
• Sponsor: University of Southampton · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 second or third relapse following a platinum based chemotherapy treatment.

Detailed description

Effective therapy for relapsed mesothelioma is an unmet need. Despite a significant number of clinical studies in the second line setting, no randomised study to date has been positive. The James Lind Alliance Priority Setting Partnership funded by the NIHR has identified immunotherapy as the number one UK research priority. To date there have been no placebo controlled randomised trials for mesothelioma using PD-L1 or PD-1 checkpoint inhibition. Early promising signals of activity relating to both PD-L1 and PD-1 targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint, and support the development of a randomised phase III trial to evaluate the efficacy of nivolumab. CONFIRM will be the first ever placebo controlled, randomised phase III trial of a PD-1 immune checkpoint inhibitor. PD-1 checkpoint inhibition has revolutionised the treatment of melanoma and is now standard of care in non-small cell lung cancer, squamous cell cancer head and neck and classical Hodgkin's lymphoma. It is being assessed rigorously in numerous other cancers making its evaluation in mesothelioma timely in CONFIRM. This trial is a randomised, double blind placebo controlled trial of patients with mesothelioma who are second or 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 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.

Conditions

• Mesothelioma

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab at a dose of 240mg as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle
OTHER	Placebo	Placebo consisting of sterile 0.9% sodium chloride as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle

Timeline

• Start date: 2017-03-28
• Primary completion: 2023-02-07
• Completion: 2023-02-07
• First posted: 2017-02-24
• Last updated: 2025-04-10

Locations

24 sites across 1 country: United Kingdom