Safety Study of Radiotherapy and Concurrent Erlotinib (Tarceva®) for Brain Metastases From a Non-Small Cell Lung Cancer
Primary Purpose
Non-Small Cell Lung Cancer, Brain Metastases
Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
erlotinib
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring erlotinib, cranial radiotherapy
Eligibility 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.
Sites / Locations
- VU University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
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
Secondary Outcome Measures
Full Information
NCT ID
NCT00536861
First Posted
September 27, 2007
Last Updated
May 27, 2008
Sponsor
Amsterdam UMC, location VUmc
1. Study Identification
Unique Protocol Identification Number
NCT00536861
Brief Title
Safety Study of Radiotherapy and Concurrent Erlotinib (Tarceva®) for Brain Metastases From a Non-Small Cell Lung Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
April 2008
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Amsterdam UMC, location VUmc
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, Brain Metastases
Keywords
erlotinib, cranial radiotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
erlotinib
Other Intervention Name(s)
Tarceva
Intervention Description
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
Primary Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suresh Senan, MD, PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Frank J Lagerwaard, MD, PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Egbert F Smit, MD, PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
Facility Information:
Facility Name
VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1007 MB
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Safety Study of Radiotherapy and Concurrent Erlotinib (Tarceva®) for Brain Metastases From a Non-Small Cell Lung Cancer
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