Vinorelbine in Mesothelioma (VIM)
This study is for patients with malignant mesothelioma of the lung lining (called pleura) who have had previous chemotherapy with a platinum-based regimen whose disease has progressed. Malignant pleural mesothelioma (MPM) is an aggressive, frequently drug resistant, and incurable disease that is increasing in incidence in the UK and worldwide. All patients with MPM will relapse following first line chemotherapy and at present, there is no standard treatment available for patients in the second line setting. The vinca alkaloid chemotherapy drug vinorelbine has shown promising activity in a single arm UK trial. However to date, there has been no randomised evaluation of vinorelbine in mesothelioma in the second line setting. In addition, there have been no trials which have looked at underlying molecular changes in mesothelioma which may predict vinorelbine efficacy; This might allow vinorelbine to be used in patients only where there is a chance of benefit. Studies suggest that vinorelbine requires a gene called BRCA1 (shown to be absent in 38% of mesothelioma cases) in order to induce cell death in mesothelioma. The VIM trial aims to establish whether vinorelbine in patients with MPM helps them live longer and whether the BRCA1 gene is helpful in selecting patients most likely to benefit from treatment.
Patients will be randomised (1:2) to receive either active symptom control (ASC) (which is all supportive care deemed necessary for pain management excluding disease modifying treatment) or ASC with vinorelbine. Patients will continue vinorelbine treatment until evidence of disease progression (or unacceptable toxicity to the drug or patient withdrawal). If vinorelbine activity is demonstrated, we will use the results from this trial to inform the design of a future phase III trial.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Randomised Phase II Trial of Oral Vinorelbine as Second Line Therapy for Patients With Malignant Pleural Mesothelioma|
- Overall Survival [ Time Frame: 2 years ]Anti-tumour activity of vinorelbine will be measured by overall survival, time from randomisation to death.
- Progression Free Survival [ Time Frame: 2 years ]Anti-tumour activity of vinorelbine will also be measured by progression free survival. We will document time from randomisation to any disease progression and/or death, defined according to strict RECIST v1.1. Lesions will be compared with baseline measurements to assess progression
- Number of serious adverse events reported [ Time Frame: 2 years ]The toxicity profile of oral vinorelbine in this setting will be used to assess safety. An independent data monitoring committee will convene and assess safety 6 months after the first patient has been randomised. If the trial is deemed safe to continue then safety will be assessed again approx every 6 months. Toxicity data will be assessed alongside serious adverse events.
- BRCA1 status in blood and tumour samples [ Time Frame: 2 years ]Tumour and blood samples will be collected for future translational research. BRCA1 expression as a putative predictor of vinorelbine sensitivity will be measured primarily in the samples.
|Actual Study Start Date:||March 1, 2016|
|Estimated Study Completion Date:||December 1, 2018|
|Estimated Primary Completion Date:||March 1, 2018 (Final data collection date for primary outcome measure)|
Placebo Comparator: Active Symptom Control
Active symptom control includes palliative care and standard care methods used to manage symptoms
|Other: Active Symptom Control|
Active Comparator: Vinorelbine
Active symptom control (ASC) as per local practice plus vinorelbine administered at a dose of 60mg/m2 orally on day 1, day 8 and day 15 on a 3- weekly cycle, incrementing to 80mg/m2 weekly on a 3-weekly cycle in the absence of any significant toxicity for subsequent cycles. Patients will continue chemotherapy until evidence of radiological progression (or unacceptable toxicity or patient withdrawal).
Vinorelbine was first licensed in the UK for Non-Small Cell Lung Cancer (NSCLC) and advanced breast cancer in 1997. Vinorelbine (Navelbine®) is a semi-synthetic, third generation, vinca alkaloid. The cytotoxic effect of vinorelbine is through the disruption of mitotic spindle formation, blocking mitosis at the G2-M stage resulting in cell death.
Other Name: Navelbine
Please refer to this study by its ClinicalTrials.gov identifier: NCT02139904
|Contact: Georgina Gardner||02920 687950||VIM@cardiff.ac.uk|
|Contact: Angela Casbard||02920 687470||casbardac@.cf.ac.uk|
|Wales Cancer Trials Unit||Recruiting|
|Cardiff, United Kingdom, CF14 4YS|
|Contact: Georgina Gardner 02920 687950 VIM@cardiff.ac.uk|
|Contact: Lisette Nixon, PhD 029 20687458 NixonLS@cardiff.ac.uk|
|Principal Investigator: Prof Dean Fennell|
|Study Chair:||Dean Fennell, Professor||University of Leicester|