Clinical trial NCT00831545: 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)
Official title: Multicenter Phase 2 Evaluation of Temozolomide for Treatment of Brain Metastases of Either Malignant Melanoma, Breast and Non-small Cell Lung Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastases of Central Nervous System
Melanoma
Breast Neoplasm
Carcinoma, Non-Small-Cell Lung
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2009-01-29
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Best response related to brain metastases observed during the study period.
timeFrame: 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 outcomes:
measure: Progression-free survival, brain progression-free survival, and overall survival.
timeFrame: 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.
measure: Adverse events according to NCI CTC grading system of toxicity.
timeFrame: Throughout the study.
Other outcomes:
Locations:
Study officials:
References:
citation: Siena S, Crino L, Danova M, Del Prete S, Cascinu S, Salvagni S, Schiavetto I, Vitali M, Bajetta E. Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study. Ann Oncol. 2010 Mar;21(3):655-661. doi: 10.1093/annonc/mdp343. Epub 2009 Sep 18.