Radical Lung Radiotherapy Plus Nelfinavir (NelfLung)
The aim of this clinical trial is to test whether the drug nelfinavir, which can increase the effectiveness of radiotherapy, can be given safely at the same time as a full dose of radiotherapy for lung cancer.
It is thought that one way that nelfinavir works is through causing changes in the blood vessels within tumours. The status of tumour blood vessels and the blood flow through them will be investigated during the trial using special imaging techniques. The dose of radiation used in this trial is greater than that used in previous trials with nelfinavir in other disease settings and the response of normal lung to the combination of nelfinavir plus radiation is unknown. Therefore, a low dose of nelfinavir will be given to the first few patients that participate and will be gradually increased in subsequent groups of patients provided that no worrying side effects are identified. There is a single report of serious side-effects in an AIDs patient who was treated with radiotherapy for lung cancer when he was also taking nelfinavir. However, in this case nelfinavir was taken at a dose 3-fold higher than the highest dose level to be tested in this trial. An important goal of this trial is to select the optimum dose of nelfinavir to be used in combination with lung radiotherapy, that can then be tested more extensively in future trials.
The radiotherapy treatment in this trial has been carefully designed to minimise the amount of healthy lung that receives radiation. Some specialised imaging techniques will be used during radiotherapy planning and delivery to help ensure that the lung cancer is targeted very precisely by radiation and that normal lung is avoided as much as possible.
One effect of nelfinavir is to interfere with the function of a particular protein in cells (called AKT). The degree to which this happens can be measured in cells from blood or tissue samples. Therefore, another aim of the study is to investigate AKT and related proteins, to check whether nelfinavir is having the predicted effect.
Radiation: Radical Radiotherapy
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Study of the HIV Protease Inhibitor, Nelfinavir, Given Concomitantly With Radical Radiotherapy (RT) for the Treatment of Non-Small Cell Lung Cancer (NSCLC)|
- maximum tolerated dose [ Time Frame: One year ] [ Designated as safety issue: Yes ]To establish the maximum tolerated dose of nelfinavir in combination with radical radiotherapy for patients with non-small cell lung cancer
- Number of participants with adverse events [ Time Frame: One year ] [ Designated as safety issue: Yes ]To assess the safety profile of combined nelfinavir together with radiotherapy in patients with NSCLC.
- Radiotherapy control rate [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]To determine in-field radiotherapy treatment control rate at 3 and 12 months post treatment.
|Study Start Date:||February 2012|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Experimental: Nelfinavir plus radical radiotherapy
Nelfinavir given in combination with radical RT
Nelfinavir tablets BD 7 days per week from D-7 of starting radiotherapy until completion of radiotherapy on D47. 3 dose levels: 750 mg bd; 1000 mg bd; and 1250 mg bd.
Other Name: Viracept®Radiation: Radical Radiotherapy
Total dose of 66 Gy delivered in 33 fractions (2.0 Gy/fraction) to the primary tumour plus a margin.
|Oxford Radcliffe NHS Trust|
|Oxford, Oxfordshire, United Kingdom, OX3 9DU|
|Principal Investigator:||Katherine Vallis||University of Oxford and Oxford Radcliffe NHS Trust|