Purpose: Mesothelioma is a relatively rare cancer which is becoming more common. It can affect one of two areas; the pleura (the lining of the lung) or the peritoneum (the lining of the abdomen). Cancer affecting the pleura is the more common of these and is called Pleural Mesothelioma. This is most commonly caused by exposure to asbestos.
Unfortunately mesothelioma is usually diagnosed at an advanced stage and so treatment is based around controlling the disease and managing the symptoms, rather than curing the disease.
The standard treatment for Advanced Malignant Pleural Mesothelioma is a combination of two anticancer drugs; Pemetrexed and Cisplatin.
The trial will look into whether there are benefits of adding a third drug called Vorinostat to the treatment.
- Phase II only – Arm I: Active Comparator
- If the patient is randomised into the Vorinostat arm they will be given Pemetrexed (500mg/m2 iv) and Cisplatin (75mg/m2 iv) on day one of a 21 day cycle plus the dose of Vorinostat determined in the phase I study.
- Interventions:
- Drug: Cisplatin.
Cisplatin (75mg/m2 iv) wil be administered on day one of a 21 day cycle for up to 6 cycles - Drug: Pemetrexed.
Patients will be given Pemetrexed (500mg/m2 iv) on day one of a 21 day cycle for up to 6 cycles - Drug: Vorinostat.
The dose and frequency of vorinostat will be determined in the Phase I study. Vorinostat will be given concurrently with Cisplatin/Pemetrexed.
- Drug: Cisplatin.
- Phase II only – Arm 2: Placebo Comparator
- If the patient is randomised into the placebo arm they will be given Pemetrexed (500mg/m2 iv) and Cisplatin (75mg/m2 iv) on day one of a 21 day cycle with the placebo for the same number of days as in the vorinostat arm.
- Interventions:
- Drug: Cisplatin.
Cisplatin (75mg/m2 iv) wil be administered on day one of a 21 day cycle for up to 6 cycles - Drug: Pemetrexed.
Patients will be given Pemetrexed (500mg/m2 iv) on day one of a 21 day cycle for up to 6 cycles - Drug: Placebo.
Patients randomised into the placebo arm of the trial will receive Cisplatin and Pemetrexed as standard as well as placebo.
- Drug: Cisplatin.
