Radical Lung Radiotherapy Plus Nelfinavir (NelfLung)

June 22, 2016 updated by: Linda Ward, Oxford University Hospitals NHS Trust

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)

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • Oxford Radcliffe NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nelfinavir plus radical radiotherapy
Nelfinavir given in combination with radical RT
Drug: nelfinavir
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 Names:
  • Viracept®
Radiation: Radical Radiotherapy
Total dose of 66 Gy delivered in 33 fractions (2.0 Gy/fraction) to the primary tumour plus a margin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
maximum tolerated dose
Time Frame: One year
To establish the maximum tolerated dose of nelfinavir in combination with radical radiotherapy for patients with non-small cell lung cancer
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: One year
To assess the safety profile of combined nelfinavir together with radiotherapy in patients with NSCLC.
One year
Radiotherapy control rate
Time Frame: 3 and 12 months
To determine in-field radiotherapy treatment control rate at 3 and 12 months post treatment.
3 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oxford University Hospitals NHS Trust

Investigators

  • Principal Investigator: Katherine Vallis, University of Oxford and Oxford Radcliffe NHS Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

July 18, 2011

First Submitted That Met QC Criteria

October 4, 2011

First Posted (Estimate)

October 6, 2011

Study Record Updates

Last Update Posted (Estimate)

June 23, 2016

Last Update Submitted That Met QC Criteria

June 22, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EP-TSC-651

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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