NCT01353482

A Phase I/II Study of First Line Vorinostat With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Mesothelioma is a rapidly lethal cancer which is increasing in incidence year on year. A projected doubling of cases has been predicted within the next two decades in Europe and the disease is usually diagnosed only after it has become advanced. As yet the standard treatment for advanced mesothelioma, chemotherapy (cytotoxic drugs), is only for disease control and symptom management. A Phase I study of a drug called Vorinostat recently looked in to its effect, when given with standard cytotoxic drugs, on advanced solid tumours. The data for this study showed that this treatment caused a response in the tumours of patients with mesothelioma. The study aims to examine the efficacy and safety of first-line vorinostat when used concurrently with cisplatin/pemetrexed. In the proposed trial, we will initially conduct an initial run-in phase I study, to find the maximum tolerated dose, before embarking on the randomised phase II trial. The study is therefore in two stages: Phase I study: to find the maximum tolerated dose of vorinostat in this patient group. Both safety (ie the observed number of Dose Limiting Toxicities per cohort and the overall toxicity profile) and the number of chemotherapy cycles administered will be used to determine the final dose of vorinostat to be used in the subsequent phase II study. Randomised Phase II study: to evaluate the efficacy and safety of vorinostat (using the dose from the phase I study) versus placebo in combination with cisplatin and pemetrexed. The Phase II study will use a placebo and double-blinding to ensure that neither the patient nor the research team are aware of the allocated treatment, which should allow for accurate comparison of the two treatment arms and reduce the potential for researcher bias. Patients will be randomized 1:1 to the two treatment arms.

Conditions

• Malignant Pleural Mesothelioma

Interventions

Type	Name	Description
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	Placebo	Patients randomised into the placebo arm of the trial will receive Cisplatin and Pemetrexed as standard as well as placebo.

Timeline

• First posted: 2011-05-13
• Last updated: 2012-03-22