Safety and Tolerability of Low-Dose Temozolomide During Whole Brain Radiation in Patients With Cerebral Metastases From Non-Small-Cell Lung Cancer (Study P04071)(TERMINATED)

Randomized Phase II Study: Temozolomide (TMZ) Concomitant to Radiotherapy Followed by Sequential TMZ in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients With Central Nervous System (CNS) Metastasis Versus Radiotherapy Alone

This is a phase II, randomized, multicenter, open-label study designed to assess the safety and tolerability of concomitant chemotherapy with low-dose temozolomide during whole brain radiation and later on at 14 days on/14 days off schedule in patients with cerebral metastases from non-small cell lung cancer (NSCLC). The response to temozolomide will be evaluated by clinical follow up and Magnetic Resonance Imaging (MRI) performed every 2 months. Progression-free survival at 6 months, duration of overall survival, and quality of life will also be evaluated.

Inclusion Criteria:

• Prior histologic confirmation of non-small cell lung cancer (NSCLC).
• Optional: NSCLC histologic confirmation of metastasis of NSCLC.
• Presence of unidimensionally measurable disease in the brain.
• No previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin.
• Age: >18 years.
• Subjects must not have systemic disease that in the opinion of the investigator is in immediate need of chemotherapy
• Karnofsky Performance status >=70%.
• Absolute neutrophil count (ANC) >1,500/mm^3, platelets >100,000/mm^3, hemoglobin >8 g/dL.
• Serum creatinine and bilirubin <1.5 times upper normal limit of testing laboratory.
• Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) <3 times upper limit of testing laboratory.
• Palliative radiation therapy to thorax and bone or other organs (except brain) is acceptable.
• Prior neurosurgery >2 weeks from initiating treatment with temozolomide.
• Cortisone medication stable or decreasing within 2 weeks prior to initiating treatment with temozolomide.
• Patient is not pregnant or nursing and is advised and willing to use an effective method of contraception.
• Written informed consent.

Exclusion Criteria:

• Chemotherapy or biologic therapy within four weeks prior to initiating therapy with temozolomide.
• Prior radiation therapy for brain <4 weeks from initiating therapy with temozolomide.
• Surgery within two weeks prior to temozolomide administration.
• Recursive Partitioning Analysis (RPA) class III
• Patients with a single brain metastasis amenable to radiosurgery of resection
• Known Human Immunodeficiency Virus (HIV) disease.
• Acute infection requiring intravenous antibiotics.
• Any reason making compliance to the protocol improbable.