Radiation Therapy and Stereotactic Radiosurgery With or Without Temozolomide or Erlotinib in Treating Patients With Brain Metastases Secondary to Non-Small Cell Lung Cancer
Condition: Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer AJCC v7
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Neoplasms
Intervention: 3-Dimensional Conformal Radiation Therapy; Erlotinib Hydrochloride; Stereotactic Radiosurgery; Temozolomide
Intervention description: Patients undergo radiation therapy once daily for approximately 3 weeks; Given orally; Patients undergo surgery after radiation therapy; Given orally
Intervention MeSH terms: Temozolomide; Erlotinib Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 126.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial is studying whole-brain radiation therapy and stereotactic
      radiosurgery with or without temozolomide or erlotinib to see how well they work compared to
      whole-brain radiation therapy and stereotactic radiosurgery in treating patients with brain
      metastases secondary to non-small cell lung cancer. Radiation therapy uses high-energy x-rays
      to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the
      tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as
      temozolomide, work in different ways to stop tumor cells from dividing so they stop growing
      or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for
      their growth and by blocking blood flow to the tumor. It is not yet known whether radiation
      therapy and stereotactic radiosurgery are more effective with or without temozolomide or
      erlotinib in treating brain metastases.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed non-small cell lung cancer

          -  One to 3 intraparenchymal brain metastases by contrast-enhanced MRI, meeting the
             following criteria:

               -  Well circumscribed tumor(s)

               -  Maximum diameter ≤ 4.0 cm

                    -  If multiple lesions are present and one lesion is at the maximum diameter,
                       the other lesions must not exceed 3.0 cm in maximum diameter

               -  No metastases within 10 mm of the optic apparatus such that a portion of the
                  optic nerve or chiasm would be included in the high-dose stereotactic
                  radiosurgery boost field

               -  No metastases in the brainstem, midbrain, pons, or medulla

          -  No prior complete resection of all known brain metastases

               -  Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum
                  diameter

          -  No clinical or radiographic evidence of progression (other than study lesion[s])
             within the past month

               -  Patients with brain metastases at initial presentation do not require 1 month of
                  scans documenting stable disease

          -  Stable extracranial metastases allowed

               -  No known or pre-existing liver metastases

          -  No leptomeningeal metastases by MRI or cerebrospinal fluid evaluation

          -  Synchronous brain metastases at initial diagnosis allowed

          -  Performance status - Zubrod 0-1

          -  Hemoglobin ≥ 8 g/dL

          -  Absolute neutrophil count ≥ 1,000/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  AST < 2 times upper limit of normal (ULN)

          -  Alkaline phosphatase < 2 times ULN unless due to elevated bone metastases

          -  Total bilirubin normal

          -  Lactic dehydrogenase < 2 times ULN

          -  Creatinine < 1.5 times ULN

          -  No clinically active interstitial lung disease

               -  Chronic stable asymptomatic radiographic changes allowed

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  HIV negative

          -  Neurologic function status 0-2

          -  No other major medical illness or psychiatric impairment that would preclude study
             participation

          -  No history of allergic reaction attributed to compounds of similar chemical or
             biologic composition to erlotinib or temozolomide

          -  No concurrent immunotherapy

          -  No concurrent biologic therapy, excluding growth factors and epoetin alfa

          -  No prior temozolomide or erlotinib

          -  No other concurrent chemotherapy during study radiotherapy

               -  Other concurrent chemotherapy allowed after study radiotherapy, except for the
                  following:

                    -  Temozolomide or erlotinib (arm I only)

                    -  Erlotinib (arm II only)

                    -  Temozolomide (arm III only)

          -  No prior cranial radiotherapy

          -  No concurrent intensity-modulated radiotherapy

          -  Concurrent radiotherapy to painful bone lesions allowed

               -  No concurrent radiotherapy to more than 15% of bone marrow

          -  No other concurrent therapy for brain metastases unless a recurrence is detected

          -  More than 30 days since prior investigational drugs

          -  No concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any
             of the following (for patients randomized to receive erlotinib):

               -  Phenytoin

               -  Carbamazepine

               -  Rifampin

               -  Phenobarbital

               -  Primidone

               -  Oxcarbazepine

          -  No other concurrent investigational drugs

          -  No concurrent Hypericum perforatum (St. John's wort)

          -  No drugs that alter gastric pH (e.g., proton pump inhibitors or H2 antagonists) within
             4 hours after erlotinib administration (arm III patients only)