Temozolomide as a Prophylaxis Against Brain Recurrence in Participants With Metastatic Breast Cancer (P05225 AM2)

Study Overview
=================
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).

Official Title
-----------------
Temozolomide in Metastatic Breast Cancer Patients at High Risk of Brain Recurrence: Impact on the Incidence of Brain Metastases (STOP)

Conditions
-----------------
Breast Neoplasm, Brain Neoplasm, Second Neoplasm

Intervention / Treatment
-----------------
* Drug: temozolomide


Participation Criteria
=================
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide<br> | Drug: temozolomide<br>* Capsules to equal 75 mg/m^2, orally, daily for 6 weeks, in 3 eight-week cycles<br>|
| No Intervention: Observational<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Recurrence of Brain Metastases | The analysis could not be performed due to low enrollment. | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days With Progression-free Survival (PFS) | PFS was defined as the time interval from randomization to objective tumor progression or death from any cause. The analysis could not be performed due to low enrollment. | 24, 38, and 52 weeks | 
| Number of Days With Disease-free Survival (DFS) | DFS was defined as the time interval from randomization to any relapse (loco-regional, contra-lateral, and/or distant). The analysis could not be performed due to low enrollment. | 24, 38, and 52 weeks | 
| Number of Days With Distant Disease-free Survival (DDFS) | DDFS was defined as the time interval from randomization to only distant metastases (for example, bone, visceral organ, brain). The analysis could not be performed due to low enrollment. | 24, 38, and 52 weeks | 
| Number of Days With Brain Recurrence-free Survival (BRFS) | BRFS was defined as the time interval from randomization to the appearance of brain metastases. The analysis could not be performed due to low enrollment. | 24,38, and 52 weeks | 
| Number of Days on Temozolomide Treatment | This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed. | Baseline to 24 Weeks | 
| Total Dose of Temozolomide Taken | This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed. | Baseline to 24 Weeks | 
| Number of Participants Who Had at Least One Dose Reduction During Treatment | This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed. | Baseline to 24 Weeks | 
| Number of Participants Who Had at Least One Treatment Omission During Treatment | This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed. | Baseline to 24 Weeks | 
| Number of Participants Who Completed the Third Cycle of Treatment | This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed. | Baseline to 24 Weeks |