Malignant pleural mesothelioma (MPM) is a rapidly lethal cancer arising from the parietal pleural mesothelium, and is associated with exposure to asbestos. Once a rare disease, it is increasing in incidence in the UK and is presently more common than cervical cancer. MPM is characterized by local invasion of adjacent structures including the chest wall, mediastinum, diaphragm and pericardium resulting in progressive shortness of breath. Median survival with best supportive care alone is approximately 6-9 months and most cases of mesothelioma present in the advanced setting. Therefore this trial will be looking at whether a new drug, Ganetespib has any improvement on survival for these types of patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
IV, Using dose from Phase I
UCL Cancer Trials Centre
London, United Kingdom
Maximum Tolerated Dose of Ganetespib
Primary endpoint (phase I): Dose-limiting toxicities during Cycles 1 \& 2; and number of cycles of pemetrexed-cisplatin given. The Phase I trial will consist of three ganetespib dose cohorts, each with 3 or 6 patients: * Cohort 1: 100mg/m2 IV on day 1 and day 15 of each cycle * Cohort 2: 150mg/m2 IV on day 1 and day 15 of each cycle * Cohort 3: 200mg/m2 IV on day 1 and day 15 of each cycle There will be additional patients to be treated with carboplatin (AUC5) instead of cisplatin. If treatment with carboplatin is confirmed to be safe and tolerable, the option of treating patients with either cisplatin or carboplatin during phase II will be taken. The evaluation will be done using an accelerated titrated phase I design. Primary endpoint (phase II): Progression free survival
Time frame: 6 Months
Progression Free Survival
Secondary endpoints (phase I): * To examine the number of cycles of pemetrexed/platinum chemotherapy administered. * To examine the objective tumour response according to meso-modified RECIST, and the overall response rate. Secondary endpoints (phase II): * To examine the frequency of all Adverse Events graded by NCI-CTCAE version 4, in particular those with grade 3 or 4 events. * To examine the objective tumour response according to meso-modified RECIST, and the overall response rate. * To examine overall survival.
Time frame: 24 Months
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