Radical Lung Radiotherapy Plus Nelfinavir (NelfLung)

This study has been withdrawn prior to enrollment.
(failed to recruit, no suitable patients)
Sponsor:
Information provided by (Responsible Party):
Linda Ward, Oxford University Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01447589
First received: July 18, 2011
Last updated: March 28, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: nelfinavir
Radiation: Radical Radiotherapy
Phase 1
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Oxford University Hospitals NHS Trust:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 0
Study Start Date: February 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01447589

Locations
United Kingdom
Oxford Radcliffe NHS Trust
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Sponsors and Collaborators
Oxford University Hospitals NHS Trust
Investigators
Principal Investigator: Katherine Vallis University of Oxford and Oxford Radcliffe NHS Trust
  More Information

No publications provided

Responsible Party: Linda Ward, QA Coordinator, Cancer Centre, Oxford University Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01447589     History of Changes
Other Study ID Numbers: EP-TSC-651
Study First Received: July 18, 2011
Last Updated: March 28, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Oxford University Hospitals NHS Trust:
Radiosensitiser

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Protease Inhibitors
Nelfinavir
HIV Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014