Radical Lung Radiotherapy Plus Nelfinavir (NelfLung)
Primary Purpose
Lung Cancer
Status
Withdrawn
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
nelfinavir
Radical Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Lung Cancer focused on measuring Radiosensitiser
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed NSCLC except bronchoalveolar cancer
- Patients deemed suitable for radical RT according to local policy
- TNM stage T1-2, N0-1, M0 plus patients with local recurrence
- Adequate lung function as defined by protocol
- Age ≥ 18 years
- ECOG performance status 0-2
- Written informed consent
- Patient able and willing to comply with all protocol requirements
Exclusion Criteria:
- History of other active invasive malignancy (excluding non-melanoma skin cancer and in situ carcinoma of the cervix), where the extent of disease or treatment for that condition may interfere with the study endpoints
- Previous RT to the chest
- Chemotherapy, immunotherapies or investigational medicinal products within 4 weeks of the start of nelfinavir treatment. Ie any neoadjuvant treatment must be completed 4 weeks prior.
- Liver impairment (serum bilirubin ≥ 2 times upper limit of normal, serum AST ≥ 2 times the upper limit of normal)
- Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used. Contraceptives that contain norethisterone or ethinylestradiol must be replaced by other contraceptive measures
- Concurrent use of contraindicated drugs that cannot be substituted or discontinued 2 weeks or more prior to the start of trial treatment
- Known hypersensitivity to nelfinavir or any of its excipients
- Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results
Sites / Locations
- Oxford Radcliffe NHS Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nelfinavir plus radical radiotherapy
Arm Description
Nelfinavir given in combination with radical RT
Outcomes
Primary Outcome Measures
maximum tolerated dose
To establish the maximum tolerated dose of nelfinavir in combination with radical radiotherapy for patients with non-small cell lung cancer
Secondary Outcome Measures
Number of participants with adverse events
To assess the safety profile of combined nelfinavir together with radiotherapy in patients with NSCLC.
Radiotherapy control rate
To determine in-field radiotherapy treatment control rate at 3 and 12 months post treatment.
Full Information
NCT ID
NCT01447589
First Posted
July 18, 2011
Last Updated
June 22, 2016
Sponsor
Oxford University Hospitals NHS Trust
1. Study Identification
Unique Protocol Identification Number
NCT01447589
Brief Title
Radical Lung Radiotherapy Plus Nelfinavir
Acronym
NelfLung
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Withdrawn
Why Stopped
failed to recruit, no suitable patients
Study Start Date
February 2012 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oxford University Hospitals NHS Trust
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
Radiosensitiser
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nelfinavir plus radical radiotherapy
Arm Type
Experimental
Arm Description
Nelfinavir given in combination with radical RT
Intervention Type
Drug
Intervention Name(s)
nelfinavir
Other Intervention Name(s)
Viracept®
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Radical Radiotherapy
Intervention Description
Total dose of 66 Gy delivered in 33 fractions (2.0 Gy/fraction) to the primary tumour plus a margin.
Primary Outcome Measure Information:
Title
maximum tolerated dose
Description
To establish the maximum tolerated dose of nelfinavir in combination with radical radiotherapy for patients with non-small cell lung cancer
Time Frame
One year
Secondary Outcome Measure Information:
Title
Number of participants with adverse events
Description
To assess the safety profile of combined nelfinavir together with radiotherapy in patients with NSCLC.
Time Frame
One year
Title
Radiotherapy control rate
Description
To determine in-field radiotherapy treatment control rate at 3 and 12 months post treatment.
Time Frame
3 and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed NSCLC except bronchoalveolar cancer
Patients deemed suitable for radical RT according to local policy
TNM stage T1-2, N0-1, M0 plus patients with local recurrence
Adequate lung function as defined by protocol
Age ≥ 18 years
ECOG performance status 0-2
Written informed consent
Patient able and willing to comply with all protocol requirements
Exclusion Criteria:
History of other active invasive malignancy (excluding non-melanoma skin cancer and in situ carcinoma of the cervix), where the extent of disease or treatment for that condition may interfere with the study endpoints
Previous RT to the chest
Chemotherapy, immunotherapies or investigational medicinal products within 4 weeks of the start of nelfinavir treatment. Ie any neoadjuvant treatment must be completed 4 weeks prior.
Liver impairment (serum bilirubin ≥ 2 times upper limit of normal, serum AST ≥ 2 times the upper limit of normal)
Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used. Contraceptives that contain norethisterone or ethinylestradiol must be replaced by other contraceptive measures
Concurrent use of contraindicated drugs that cannot be substituted or discontinued 2 weeks or more prior to the start of trial treatment
Known hypersensitivity to nelfinavir or any of its excipients
Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine Vallis
Organizational Affiliation
University of Oxford and Oxford Radcliffe NHS Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oxford Radcliffe NHS Trust
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
12. IPD Sharing Statement
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Radical Lung Radiotherapy Plus Nelfinavir
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