A Phase III Trial Comparing Whole Brain Radiation (WBRT) and Stereotactic Radiosurgery (SRS) Alone Versus With Temozolomide or Erlotinib in Patients With Non-Small Cell Lung Cancer and 1-3 Brain Metastases
1. Histologically confirmed non-small cell lung cancer with the presence of 1-3
intraparenchymal brain metastases.
2. A contrast-enhanced MRI demonstrating the presence of 1-3 brain metastases performed
within two weeks prior to registration.
3. The contrast-enhancing intraparenchymal brain tumor must be well circumscribed and
must have a maximum diameter of ≤ 4.0 cm in any direction on the enhanced scan. If
multiple lesions are present and one lesion is at the maximum diameter, the other(s)
must not exceed 3.0 cm in maximum diameter.
4. Patients who present with symptoms of brain metastases at the time of initial
diagnosis are eligible and do not need to demonstrate one month of stable scans.
5. Age 18 years or older.
6. Zubrod 0-1
7. Neurologic Function Status 0, 1, or 2.
8. Patients may have stable extracranial metastases.
9. Contrast-enhancing CT scans of the chest, abdomen and pelvis, and bone scan to
determine the extent of extracranial malignant disease.
10. Adequate bone marrow reserve
11. Patients randomized to receive erlotinib who are on enzyme inducing seizure medicines
including phenytoin, carbamazepine, rifampicin, barbiturates must be converted to a
nonenzyme inducing anti-seizure medication. Patients on Arm 3 will not be able to
start treatment immediately if converting.
12. Patient must sign a study-specific informed consent form. If the patient’s mental
status precludes his/her giving informed consent, written informed consent may be
given by the patient’s legal representative.
1. Major medical illnesses or psychiatric impairment
2. Patients who have undergone a complete resection of all known brain
metastases.Patients who have undergone subtotal resection are eligible providing
residual disease is =/< 4.0 cm in maximum diameter.
3. Inability to obtain histologic proof of NSCLC.
4. Patients with leptomeningeal metastases documented by MRI or CSF evaluation.
5. Clinical or radiographic evidence of progression (other than the study lesion(s))
within one month prior to enrollment. (Patients who have brain metastases at initial
presentation are eligible and do not need to demonstrate one month of stable scans).
6. Patients with metastases within 10 mm of the optic apparatus so that some portion of
the optic nerve or chiasm would be included in the high dose SRS boost field.
7. Patients with metastases in the brainstem, midbrain, pons, or medulla.
8. Patients with liver metastases.
9. Previous cranial radiation.
10. Women who are pregnant or nursing
11. Patients who are HIV positive are not eligible.
12. Any evidence of clinically active interstitial lung disease
13. Treatment with a non-approved or investigational drug within 30 days before Day 1 of
14. Concomitant use of St. John’s Wort.
15. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to erlotinib and temozolomide.