Study of Maintenance Temozolomide Versus Observation in Stable or Responding Stage III/IV Non-Small Cell Lung Cancer Patients (Study P05146)

A Randomized Phase 2 Study of Maintenance Temozolomide Versus Observation in Stable or Responding Stage III/IV Non-Small Cell Lung Cancer Patients

The main objective of this study is to investigate whether administration of maintenance temozolomide following standard treatment could possibly prevent or delay the onset of brain metastases in patients with controlled non-small cell lung cancer (NSCLC).

This is a Phase 2, open-label, randomized, multicenter study of maintenance temozolomide versus observation in subjects with stable or responding stage III/IV NSCLC to be conducted in conformance with Good Clinical Practices. Subjects will be randomly assigned to a study drug (temozolomide) or observation arm. The study drug will be administered at a dose of 75 mg/m^2 PO daily for 21 consecutive days, followed by a 7-day rest period, until progression or up to a maximum of 6 cycles, whichever occurs first. Subjects completing 6 cycles of treatment will be followed up for incidence of brain metastasis for up to 2 years, or until progression.

Inclusion Criteria:

• Adult subjects (age >=18 years), of either sex, and of any race.
• Subjects must have stage IV or III with pleural and/or pericardial effusion

histologically confirmed NSCLC.

• Subjects must have completed 2-6 cycles of a standard systemic therapy, with or without radiation therapy, consisting of at least 2 anti-tumor agents as first-line treatment for Stage III/IV disease, and have documented complete response (CR), partial response (PR), or stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST).
• Response must be confirmed within 4-8 weeks of completing first-line chemotherapy. Study treatment must begin within 12 weeks of completing first-line chemotherapy.
• Female subjects of childbearing potential or male subjects with female partner of childbearing potential must agree to use a medically accepted method of contraception or be surgically sterilized prior to Screening, while receiving study drug, and for 30 days after stopping study drug. Female subjects of childbearing potential must have a negative pregnancy test confirmed prior to dosing with study drug.
• Subjects must be free of any clinically relevant disease (other than stage III/IV NSCLC) that would, in the principal investigator and/or Sponsor's opinion, interfere with the conduct of the study or study evaluations.
• Subjects must be able to adhere to the dosing and visit schedules, and agree to report medication taken, concomitant medications, and adverse events (AEs).
• Eastern Cooperative Oncology Group (ECOG) performance status <=2.
• Clinical laboratory tests (complete blood count [CBC], serum chemistries) must be obtained within 14 days prior to randomization and meet specified criteria.

Exclusion Criteria:

• Brain metastases documented on post-chemotherapy magnetic resonance imaging (MRI).
• Documented history of brain metastases.
• Subject has received more than one prior anti-tumor regimen for Stage III/IV disease. "Regimen" refers to single drug or planned combination of two or more anti-tumor therapies. Bevacizumab (Avastin®) as part of a planned sequence of therapy after first-line platinum-containing double regimen is not considered a second regimen. Neo-adjuvant treatment for resectable subjects is not considered a second regimen.
• Subject has used any investigational product within 4 weeks prior to enrollment.
• Subject is currently receiving immunotherapy or chemotherapy, cytotoxic or targeted therapy as treatment for active systemic disease. Bevacizumab (Avastin®) as part of the prescribed standard first-line regimen is allowed.
• Female who is pregnant, or intends to become pregnant, during the study.
• Subject is in a situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
• Subject is currently participating in any other clinical study, with the exception of observational long-term follow-up.
• Subject is allergic to, or has sensitivity to, the study drug or its excipients.
• Documented symptomatic, progressive or new bone metastases following the first-line chemotherapy with or without radiation therapy (biphosphonate use for prophylaxis or as a maintenance therapy is allowed).
• No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for 5 years.