Pleural Mesothelioma

CheckpOiNt Blockade For Inhibition of Relapsed Mesothelioma (CONFIRM)

Purpose: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.

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CAR T Cells in Mesothelin Expressing Cancers

Purpose: Phase I study to establish safety and feasibility of intravenous or intrapleural administered lentiviral transduced huCART-meso cells with or without lymphodepletion. Intravenous administration of huCART-meso cells is planned with or without cyclophosphamide as lymphodepleting chemotherapy.

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Pembrolizumab With or Without Anetumab Ravtansine in Treating Patients With Mesothelin-Positive Pleural Mesothelioma

Purpose: This randomized phase I/II trial studies the side effects and how well pembrolizumab with or without anetumab ravtansine work in treating patients with mesothelin-positive pleural mesothelioma. Monoclonal antibodies, such as anetumab ravtansine and pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

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Phase II MEDI4736 in Combination With Chemotherapy for First-Line Treatment of Unresectable Mesothelioma (PrE0505)

Purpose: Patients with pleural mesothelioma that can not be surgically removed will receive durvalumab, in combination with standard chemotherapy of pemetrexed and cisplatin as first-line treatment.
Durvalumab is a type of drug called a monoclonal antibody (a type of protein). Laboratory tests show that it works by allowing the immune system to detect your cancer and reactivates the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. The purpose of this study is to see whether adding durvalumab to standard chemotherapy will improve overall survival (OS).

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Bosutinib in Combination With Pemetrexed in Patients With Selected Metastatic Solid Tumors

Purpose: This study will determine the maximum-tolerated dose (MTD) for oral bosutinib when used in combination with pemetrexed. The MTD is the highest dose of bosutinib with pemetrexed that can be given without causing severe side effects. This study will also test the safety of this combination and see what effects (good or bad) it has on participants and their cancer.

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