Radiation Therapy and Stereotactic Radiosurgery With or Without Temozolomide or Erlotinib in Treating Patients With Brain Metastases Secondary to Non-Small Cell Lung Cancer

• Status: Terminated
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Collaborator: Radiation Therapy Oncology Group
• Treatments: Dacarbazine; Erlotinib Hydrochloride; Temozolomide

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)