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)

Merck Sharp & Dohme (MSD)

Status and phase

Completed

Phase 2

Conditions

Metastases of Central Nervous System

Breast Neoplasm

Melanoma

Carcinoma, Non-Small-Cell Lung

Treatments

Drug: Temozolomide

Study type

Interventional

Funder types

Industry

Identifiers

NCT00831545

P02064

Details and patient eligibility

About

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.

Enrollment

162 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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.