CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma (CONFIRM)
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|ClinicalTrials.gov Identifier: NCT03063450|
Recruitment Status : Recruiting
First Posted : February 24, 2017
Last Update Posted : February 5, 2020
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. 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.
|Condition or disease||Intervention/treatment||Phase|
|Mesothelioma||Drug: Nivolumab Other: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||336 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Actual Study Start Date :||March 28, 2017|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2021|
Nivolumab 240mg flat dose Q2W over 30 minutes IV until disease progression, to a maximum of 12 months
Nivolumab at a dose of 240mg as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle
Other Name: Opdivo
Placebo Comparator: Placebo
Sterile 0.9% sodium chloride Q2W over 30 minutes IV until disease progression, to a maximum of 12 months
Placebo consisting of sterile 0.9% sodium chloride as a 30-minute IV infusion, on Day 1 of every 14 day treatment cycle
- Overall survival [ Time Frame: Time from randomisation to date of death from any cause, assessed up to 51 months ]
- Progression free survival (modified RECIST or RECIST 1.1) [ Time Frame: Time from randomisation to progression, assessed up to 51 months ]Length of time patients are free from disease through study completion
- Overall response rate (modified RECIST or RECIST 1.1) [ Time Frame: Time from randomisation to progression through study completion, assessed up to 51 months ]Response of disease to treatment
- Quality of life (EQ-5D-5L) [ Time Frame: At baseline, after cycles 3 and 6 (each cycle is 14 days) and 1, 6 and 12 months post progression/treatment discontinuation. ]
- Toxicity (CTCAE V4.03) [ Time Frame: At baseline, after each treatment cycle (each cycle is 14 days) and each follow up visit. Up to 30 days post progression/treatment discontinuation. ]
- Cost effectiveness (Health resource use questionnaire) [ Time Frame: Up to max. 24 months. At baseline, after cycles 3 and 6 (each cycle is 14 days) and 1, 6 and 12 months post progression/treatment discontinuation. ]
- Transnational [ Time Frame: Samples collected at baseline and optional sample at progression (assessed up to 51 months from randomisation) ]
- mutation burden with OS
- immunosuppressive landscape (immune checkpoint expression and infiltration of immune cell) and nivolumab efficacy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03063450
|Contact: Calley Middleton||023 8120 email@example.com|
|Contact: Ellice Marwood||023 8120 firstname.lastname@example.org|
|Principal Investigator:||Dean Fennell||University of Leicester|
|Principal Investigator:||Gareth Griffiths||Southampton Clinical Trials Unit, University of Southampton|