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

NCT00536861 | Completed Phase 1

• 1 other identifier: VUMC 2005/177
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer; Brain Metastases

Keywords

erlotinib; cranial radiotherapy

Outcome Measures

Primary Outcomes (1)

• To establish the safety of concurrent palliative whole brain radiotherapy and two doses of erlotinib in patients with brain metastases from NSCLC

  Until death

Study Arms (1)

1

EXPERIMENTAL

Drug: erlotinib

Interventions

erlotinib DRUG

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

Also known as: Tarceva

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1007 MB, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Suresh Senan, MD, PhD

  Amsterdam UMC, location VUmc

  STUDY CHAIR

• Frank J Lagerwaard, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• Egbert F Smit, MD, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 27, 2007
• First Posted: September 28, 2007
• Study Start: May 1, 2006
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: May 29, 2008

Record last verified: 2008-04

Locations

NL (1)