Clinical trial NCT00638963: Temozolomide as a Prophylaxis Against Brain Recurrence in Participants With Metastatic Breast Cancer (P05225 AM2)
Official title: Temozolomide in Metastatic Breast Cancer Patients at High Risk of Brain Recurrence: Impact on the Incidence of Brain Metastases (STOP)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Neoplasm
Brain Neoplasm
Second Neoplasm
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-03-19
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether temozolomide can be used as a prophylaxis against brain recurrence in participants with metastatic breast cancer.

Detailed description: Breast cancer is the second most common cause of brain metastases. Overall survival after the development of brain metastases tends to be poor (6-8 months). Over-expression of Human Epidermal Growth Factor Receptor 2 (HER-2/neu), negative estrogen receptor, and young age at diagnosis seem to be indicators of high risk for brain metastases. Temozolomide may be a good candidate for prophylactic chemotherapy because of its ability to cross the blood-brain-barrier, achieving high concentrations in the central nervous system (CNS).

Eligibility criteria: Inclusion Criteria:

* Diagnosis of metastatic breast cancer.
* Participants must have completed first line of metastatic chemotherapy and have achieved complete or partial response or disease stability for at least 6 months from the first confirmation of disease stabilization.
* No clinical sign of brain progression.
* At least one of the following 3 conditions: HER2 +++, Young age (\< 50 years), and/or estrogen receptor (ER)-/progesterone receptor (PgR)-
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
* Life expectancy ≥3 months.
* Neutrophils ≥1.5 x 10\^9/L, platelets ≥100 x 10\^9/L, hemoglobin ≥9 g/dL, lymphocytes ≥1 x 10\^9/L.
* Bilirubin level either normal or \<1.5 x ULN (upper limit of normal).
* AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤2.5 x ULN (≤5 x ULN if liver metastases are present).
* Serum creatine \<1.5 x ULN.
* Effective contraception if the risk of conception exists.

Exclusion Criteria:

* Concurrent chronic systemic immune therapy not indicated in the study protocol.
* Any investigational agent(s) within 4 weeks prior to entry.
* Participants that have completed 2nd, 3rd, or 4th line metastatic chemotherapy or participant in active chemotherapy treatment.
* Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months.
* Acute or sub acute intestinal occlusion or history of inflammatory bowel disease.
* Known Grade 3 or Grade 4 allergic reaction to any of the components of the treatment.
* Known drug abuse/alcohol abuse.
* Legal incapacity or limited legal capacity.
* Medical or psychological condition which in the opinion of the investigator would not permit the participant to complete the study or sign meaningful informed consent.
* Women who are pregnant or breastfeeding.
* Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix (participants with a previous malignancy but without evidence of disease for ≥5 years will be allowed to enter the trial).

Primary outcomes:
measure: Percent of Participants With Recurrence of Brain Metastases
timeFrame: 1 Year
Secondary outcomes:
measure: Number of Days With Progression-free Survival (PFS)
timeFrame: 24, 38, and 52 weeks
measure: Number of Days With Disease-free Survival (DFS)
timeFrame: 24, 38, and 52 weeks
measure: Number of Days With Distant Disease-free Survival (DDFS)
timeFrame: 24, 38, and 52 weeks
measure: Number of Days With Brain Recurrence-free Survival (BRFS)
timeFrame: 24,38, and 52 weeks
measure: Number of Days on Temozolomide Treatment
timeFrame: Baseline to 24 Weeks
measure: Total Dose of Temozolomide Taken
timeFrame: Baseline to 24 Weeks
measure: Number of Participants Who Had at Least One Dose Reduction During Treatment
timeFrame: Baseline to 24 Weeks
measure: Number of Participants Who Had at Least One Treatment Omission During Treatment
timeFrame: Baseline to 24 Weeks
measure: Number of Participants Who Completed the Third Cycle of Treatment
timeFrame: Baseline to 24 Weeks
Other outcomes:
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