This research study is studying a drug called atezolizumab as a possible treatment HER2-positive metastatic breast cancer (MBC) that has spread to the brain. The names of the study drugs involved in this study are: * Atezolizumab * Pertuzumab * Trastuzumab
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the combination of atezolizumab, trastuzumab, and pertuzumab for use in humans. The FDA has not approved atezolizumab for this specific disease but it has been approved for other uses. * Atezolizumab is a protein that affects the immune system by blocking the PD-L1 pathway. The PD-L1 pathway controls the body's natural immune response, but for some types of cancer the immune system does not work as it should and is prevented from attacking tumors. Atezolizumab works by blocking the PD-L1 pathway, which may help the immune system identify and catch tumor cells. * Pertuzumab and trastuzumab are targeted therapies approved by the FDA to be used alone or in combination with a chemotherapy drug to treat HER2-positive metastatic breast cancer that hasn't been treated with either trastuzumab or chemotherapy yet. * Pertuzumab and trastuzumab are called "targeted therapies" because they work by attaching themselves to specific receptors on the surface of breast cancer cells, known as HER2 receptors. When these targeted therapies attach to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by your immune system. This process allows pertuzumab and trastuzumab to help slow or stop the growth of the breast cancer. Pertuzumab and trastuzumab target different areas of the HER2 cell, so they are believed to work together more effectively. In this research study, investigators are looking to see how well the cancer responds to the combination of atezolizumab in combination with pertuzumab and trastuzumab.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
(IV) every 3 weeks
Loading dose, followed every 3 weeks thereafter by a predetermined dose in the protocol via IV
Predetermined dose per protocol via IV, weekly for 24 weeks and after every 3 weeks
Northwestern University
Chicago, Illinois, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Confirmed Overall Response Rate in CNS
The proportion of patients who had confirmed complete response or confirmed partial response, assessed using neuro-oncology-brain metastases (RANO-BM) criteria. RANO-BM assess the response of brain metastases to treatment, using MRI scan. There are four categories as results: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD), which is separately defined as disappearance of all target lesions, at least a 30% decrease in the sum of the diameters of target lesions, neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as progressive disease (PD) and at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest) or the appearance of one or more new lesions.
Time frame: Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks in the real study data
Objective Non-CNS Response Rates
The proportion of patients who had confirmed complete response or partial response, according to response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. RECIST is used to assess the response of solid tumors to treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks in the real study data
Clinical Benefit Rate in CNS at 18 Weeks
The proportion of patients who had stable disease, confirmed partial response or complete response, respectively, \>=18 weeks, according to RANO-BM criteria
Time frame: Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks in the real study data
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Patient Reported Outcomes by MDASI-BT Stratified by CBR at 18 Weeks
Evaluated by M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT). MDASI-BT assess 13 symptom items and 6 interference items from the core MDAST as well as 9 symptoms specific to brain tumors, and generate Symptom Severity Score (SSS) and Symptom Interference Score (SIS) separately. The scale of the scores are in a range of 0 to 10, where 0 represents "not present" or "not severe," and 10 represents "as bad as you can imagine" or "most severe." A higher score indicates a higher level of symptom severity. Mean of the scores are reported across groups with and without CBR at 18 weeks and in baseline, week 9 and week 24.
Time frame: 24 weeks
Patient Reported Outcomes by EQ-5D Stratified by CBR at 18 Weeks
Evaluated by EuroQol Five Dimension Questionnaire (EQ-5D) evaluations assessments to assess the general health status of patients enrolled in the study. EQ-5D scores are assessed with five dimensions with the range of 0 to 5, and a higher score indicates worse health. Mean of the scores are reported across groups with and without CBR at 18 weeks and in baseline, week 9 and week 24.
Time frame: 24 weeks
Investigator-Assessed Neurological Evaluation (NANO) Stratified by CBR at 18 Weeks
Evaluated by physician assessed Neurological Assessment in Neuro-Oncology (NANO) scale. The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during visits. The score defines overall response criteria and is with the range of 0 to 4. Higher score means worse response to the treatment. Mean of the scores are reported across groups with and without CBR at 18 weeks and in baseline, week 9 and week 24.
Time frame: 24 weeks
Clinical Benefit Rate in CNS at 24 Weeks
The proportion of patients who had stable disease, confirmed partial response or complete response, respectively, \>=24 weeks, according to RANO-BM criteria
Time frame: Participants were evaluated for response every 6 weeks for the first 24 weeks and then every 9 weeks thereafter, through study completion, an average of 24 weeks in the real study data