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)

Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00831545
• Other study ID #: P02064
• Status: Completed
• Phase: Phase 2
• First received: January 15, 2009
• Last updated: May 8, 2017
• Start date: December 1, 2000
• Est. completion date: October 20, 2006

Study information

• Verified date: May 2017
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: October 20, 2006
• Est. primary completion date: October 20, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasm
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Melanoma
• Metastases of Central Nervous System
• Neoplasm Metastasis

Intervention

Drug:
• Temozolomide
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).

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Quintiles, Inc.

References & Publications (1)

Siena S, Crinò 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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	Adverse events according to NCI CTC grading system of toxicity.		Throughout the study.