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
Overview
- Phase
- Phase 2
- Intervention
- Temozolomide and radiotherapy
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 35
- Primary Endpoint
- Number of Participants With Progression-free Survival (6 Month)
- Status
- Terminated
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
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.
Arms & Interventions
Chemotherapy with temozolomide and radiotherapy
Intervention: Temozolomide and radiotherapy
Radiotherapy alone
Intervention: Whole brain radiotherapy
Outcomes
Primary Outcomes
Number of Participants With Progression-free Survival (6 Month)
Time Frame: 6 months
The occurrence of progression will be compared between the study groups by Kaplan-Meier curves. Responsiveness to temozolomide will be evaluated by brain Magnetic Resonance Imanging (MRI)/Computed Tomography (CT), thorax CT, and Quality of Life (QoL) assessments. Progression-free is defined as \<25% increase in tumor size on CT or MRI.