Breast Neoplasm, Carcinoma, Non-Small-Cell Lung, Melanoma, Metastases of Central Nervous System
Conditions
Brief summary
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.
Interventions
DRUGTemozolomide
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).
Sponsors
Quintiles, Inc.
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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. |
Outcome results
None listed