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)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Temozolomide and radiotherapy
* Procedure: Whole brain radiotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy with temozolomide and radiotherapy<br> | Drug: Temozolomide and radiotherapy<br>* Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100 mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).<br>* Other names: Temodal, TMZ, SCH 052365;|
| Active Comparator: Radiotherapy alone<br> | Procedure: Whole brain radiotherapy<br>* 2 regimens are allowed: a) 20 fractions of 2 Gray each, administered on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Progression-free Survival (6 Month) | 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. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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temozolomide, radiotherapy