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

This study has been completed.
Sponsor:
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT00536861
First received: September 27, 2007
Last updated: May 27, 2008
Last verified: April 2008
  Purpose

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 Intervention Phase
Non-Small Cell Lung Cancer
Brain Metastases
Drug: erlotinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: May 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00536861

Locations
Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1007 MB
Sponsors and Collaborators
VU University Medical Center
Investigators
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
  More Information

No publications provided

Responsible Party: Professor S Senan, VU Medical Center
ClinicalTrials.gov Identifier: NCT00536861     History of Changes
Other Study ID Numbers: VUMC 2005/177
Study First Received: September 27, 2007
Last Updated: May 27, 2008
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:
erlotinib
cranial radiotherapy

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

ClinicalTrials.gov processed this record on August 01, 2014