Vinorelbine in Mesothelioma
Conditions
Mesothelioma
Conditions: official terms
Mesothelioma
Conditions: Keywords
Mesothelioma, Vinorelbine, BRCA1
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Vinorelbine Type: Drug
Name: Active Symptom Control Type: Other
Overall Status
Not yet recruiting
Summary
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Confirmed histological diagnosis of malignant pleural mesothelioma. The same block or 10 unstained slides should be available for translational research

2. Prior treatment with first-line standard platinum doublet based chemotherapy only

3. Evidence of disease progression according to CT scan

4. Life expectancy ≥ 3 months

5. ECOG performance status 0-2

6. Men or women aged 18 years or over

7. Willing to consent to provide blood and tissue for translational research

8. Measurable lesions by modified RECIST

9. Adequate organ function, including the following: Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, WBC >3 x 109/L, haemoglobin ≥ 100g/L, platelets ≥ 100 x 109/L; adequate liver function: Bilirubin <1.5 x ULN AST/ALT 1.5- 2.5 x ULN.

10. Patients with reproductive potential (male or female), who are sexually active during the duration of the trial or the drug washout period, should be prepared to use two effective forms of contraception throughout their participation in the trial and for at least three months after the last dose of vinorelbine.

11. Patients must provide informed consent prior to any study specific procedures.

Exclusion Criteria:

1. Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission or patients with a diagnosis of basal cell carcinoma of the skin.

2. Have received treatment with an agent that has not received regulatory approval, within 30 days of study entry.

3. Are pregnant or breastfeeding.

4. Uncontrolled CNS disease.

5. Known contraindication or hypersensitivity to vinorelbine or other vinca alkaloids or to any of the constituents

6. Any disease significantly affecting absorption

7. Previous significant surgical resection of stomach or small bowel

8. Yellow fever vaccine within 30 days of consent

9. Previous vinca alkaloid chemotherapy

10. Palliative radiotherapy within the RECIST area in the 4 weeks prior to baseline CT chest up until randomisation.

11. Patients that are unable to swallow
Location
Wales Cancer Trials Unit
Cardiff, United Kingdom
Status: Not yet recruiting
Contact: Kirsty Roberts, PhD - 02920 687201 - robertska3@cf.ac.uk
Start Date
August 2014
Completion Date
December 2016
Sponsors
Lisette Nixon
Source
Velindre NHS Trust
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page