Safety Study of Radiotherapy and Concurrent Erlotinib (Tarceva®) for Brain Metastases From a Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00536861
Recruitment Status : Completed
First Posted : September 28, 2007
Last Update Posted : May 29, 2008
Information provided by:
VU University Medical Center

Brief Summary:
Lung cancer is a leading cause of death worldwide. Brain metastases manifest as the first site of disease failure in between 15-30% of patients with non-small cell lung cancer (NSCLC). The standard treatment for patients with multiple brain metastases is whole brain radiotherapy but this results in only a modest survival of 3-6 months. Drugs that can enhance the effect of cranial irradiation (radiosensitizers) may improve the the response rates. Erlotinib (Tarceva) is an oral agent that has been registered for treatment in patients with metastatic NSCLC. Erlotinib has shown tumor activity in patients presenting with brain metastases, and preclinical studies show that it may be a radiosensitizer. As a prelude to studies investigating the combination of Erlotinib and cranial radiotherapy, the present study will be performed to evaluate the safety of combining both these treatments.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Brain Metastases Drug: erlotinib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Radiotherapy Concurrent With Erlotinib (Tarceva®) in the Treatment of Brain Metastases From Non-Small Cell Lung Cancer (NSCLC)
Study Start Date : May 2006
Actual Primary Completion Date : December 2007
Actual Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: 1 Drug: erlotinib

Level 1 : erlotinib 100 mg/day from day -7 to the time of completion of 10 fractions of cranial irradiation, followed by 150 mg/day until disease progression or toxicity

Level 2 : erlotinib 150 mg/day from day -7 before cranial irradiation, followed by 150 mg/day until disease progression or toxicity

Other Name: Tarceva

Primary Outcome Measures :
  1. To establish the safety of concurrent palliative whole brain radiotherapy and two doses of erlotinib in patients with brain metastases from NSCLC [ Time Frame: Until death ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histological or cytological confirmation of non-small cell lung cancer (NSCLC)
  • Diagnosis of brain metastases on a contrast-enhanced CT scan or Gadolinium-enhanced MRI
  • Patients who are not candidates for surgery or stereotactic radiosurgery
  • RPA Class 1 or 2 (Karnofsky performance status > 70)
  • Age > 18 years
  • No previous radiotherapy, surgery or chemotherapy for brain metastases
  • Patients must be able to take oral medication.
  • Patients should not have any unstable systemic disease except lung cancer (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease).
  • Granulocyte count > 1.5 x 109/L and platelet count > 100 x 109/L OK
  • Serum bilirubin must be < 1.5 upper limit of normal (ULN).
  • AST and/or ALT < 2 x ULN (or < 5 x ULN if clearly attributable to liver metastasis)
  • Serum creatinine < 1.5 ULN or creatinine clearance > 60 ml/min
  • Patients with reproductive potential must use effective contraception. For all females of childbearing potential a negative pregnancy test must be obtained within 72 hours before starting therapy.
  • Able to comply with study and follow-up procedures
  • Written informed consent.

Exclusion Criteria:

  • Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, hepatic, renal or metabolic disease).
  • Signs, symptoms or MRI findings consistent with leptomeningeal metastases.
  • Concomitant use of phenytoin anticonvulsant medication
  • Prior therapy with systemic anti-tumour therapy with HER1/EGFR inhibitors (as small molecule or monoclonal antibody therapy).
  • Any other malignancies in the preceding 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).
  • Any significant ophthalmological abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions. The use of contact lenses is not recommended during the study. The decision to continue to wear contact lenses should be discussed with the patient's treating Oncologist and ophthalmologist.
  • Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
  • Nursing mothers.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00536861

VU University Medical Center
Amsterdam, Netherlands, 1007 MB
Sponsors and Collaborators
VU University Medical Center
Study Chair: Suresh Senan, MD, PhD VU University Medical Center
Principal Investigator: Frank J Lagerwaard, MD, PhD VU University Medical Center
Principal Investigator: Egbert F Smit, MD, PhD VU University Medical Center

Responsible Party: Professor S Senan, VU Medical Center Identifier: NCT00536861     History of Changes
Other Study ID Numbers: VUMC 2005/177
First Posted: September 28, 2007    Key Record Dates
Last Update Posted: May 29, 2008
Last Verified: April 2008

Keywords provided by VU University Medical Center:
cranial radiotherapy

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Brain Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action