Study to Evaluate the Efficacy and Safety of Temozolomide in Subjects With Brain Metastases of Either Malignant Melanoma, Breast, or Non-small Cell Lung Cancer (P02064)

Study Overview
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Brief Summary
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The study implies a 2 step study design. Patients are enrolled into 3 separate groups for melanoma, breast, and non-small cell lung cancer. In the first step, 21 patients per disease group are enrolled. If >=2 objective responses (SD, PR, or CR) out of 21 evaluable patients are observed, enrollment continues for other 45 patients as a whole, where response will be positively evaluated if >=10 patients will respond. If <2 objective responses out of 21 evaluable patients per disease group are observed, this(ese) group(s) will no longer be treated with temozolomide.

Official Title
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Multicenter Phase 2 Evaluation of Temozolomide for Treatment of Brain Metastases of Either Malignant Melanoma, Breast and Non-small Cell Lung Cancer.

Conditions
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Metastases of Central Nervous System, Melanoma, Breast Neoplasm, Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytological/histological diagnosis of either melanoma, non-small cell lung cancer and breast; Brain metastases >=1 cm presenting or in progression following >=4 weeks time interval free from previous malignancy-specific chemotherapy, hormone therapy, or other medical therapies; Magnetic resonance imaging suspected brain metastases; patients with brain lesion(s) not univocal as brain metastases must have negative radiolabeled leukocyte brain scan to rule out infectious non-malignant disease; all neuroradiological studies (baseline and treatment outcome evaluation), except for emergency exams must be performed after 10 days of unchanged schedule of dexamethasone, and obtained in the axial-coronal-sagittal planes in T1 and T2 before and after gadolinium enhancement. Presence of al least one bidimensionally measurable and not previously irradiated metastasis. Age <=70 years. Performance status 0-2 (ECOG-WHO scale). Blood leukocytes >=3.5 x 10^9/L and platelets >=100 x 10^9/L. Bilirubin <=25 M/L. Seric transaminases <=2 x upper limit of normal values. Creatinine <=150 M/L, creatinine clearance >=60 mL/min. Signed written informed consent. Exclusion Criteria: Diabetes not allowing administration of adequate doses of dexamethasone at least during the first 2 months of treatment. Previous whole brain irradiation. Brain metastases eligible to neurosurgery or stereotactic radiation therapy. 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. Pregnant or nursing women. Acute infection requiring intravenous antibiotics. Severe vomiting or medical condition which could interfere with oral medication intake. Anticonvulsant chronic therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with melanoma<br> | Drug: Temozolomide<br>* 150 mg/m2 given once a day for 7 consecutive days (Days 1 through 7) repeated every other week until disease progression or toxicity or for a maximum of one year. After amendment, schedule was modified: a second rest week was added after the second wash-out week (Days 1 through 7, 15 through 21 every 35).<br>* Other names: SCH 52365;|
| Experimental: Subjects with breast cancer<br> | Drug: Temozolomide<br>* 150 mg/m2 given once a day for 7 consecutive days (Days 1 through 7) repeated every other week until disease progression or toxicity or for a maximum of one year. After amendment, schedule was modified: a second rest week was added after the second wash-out week (Days 1 through 7, 15 through 21 every 35).<br>* Other names: SCH 52365;|
| Experimental: Subjects with non-small cell lung cancer<br> | Drug: Temozolomide<br>* 150 mg/m2 given once a day for 7 consecutive days (Days 1 through 7) repeated every other week until disease progression or toxicity or for a maximum of one year. After amendment, schedule was modified: a second rest week was added after the second wash-out week (Days 1 through 7, 15 through 21 every 35).<br>* Other names: SCH 52365;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response related to brain metastases observed during the study period. |  | After 2 months of initial treatment. If response or stable disease evaluations were performed every 3 months. Subsequently, an additional check up was added by amendment: a follow up check was performed after 4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival, brain progression-free survival, and overall survival. |  | After 2 months of initial treatment. If response or stable disease evaluations were performed every 3 months. Subsequently, an additional check up was added by amendment: a follow up check was performed after 4 weeks. | 
| Adverse events according to NCI CTC grading system of toxicity. |  | Throughout the study. |