This is a single arm, Phase IIA clinical trial assessing the safety and efficacy of atezolizumab in combination with paclitaxel, trastuzumab, and pertuzumab in 50 patients with locally advanced, unresectable, or metastatic HER2-overexpressing breast cancer. Due to concerns that corticosteroids may have a negative effect on tumor immunity expected with addition of atezolizumab to the standard of care regimen, patients will receive premedication with dexamethasone only for weeks 1 and 2 of the weekly paclitaxel, and then corticosteroid premedication will be discontinued subsequently. Patients must have pathologically confirmed HER2-overexpressing breast cancer that is locally recurrent, unresectable, or metastatic, with measurable disease as defined by RECIST v1.1. Tumor measurements and bone scans will be performed every 9 weeks while patients are on study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Monoclonal antibody
Chemotherapy
Monoclonal antibody
Monoclonal antibody
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Number of participants with treatment-related adverse events
Treatment-related adverse events will be assessed by CTCAE v4.0
Time frame: Up to 5 years after stopping study treatment
Antitumor activity of atezolizumab plus the standard regimen of paclitaxel, trastuzumab, and pertuzumab
Antitumor activity will be measured by RECIST v1.1
Time frame: An average of 18 weeks
Overall survival (OS)
OS is defined as the time from initiation of treatment until death from any cause or end of the study period, whichever occurs first.
Time frame: Up to 5 years after the last patient stops treatment
Time to tumor progression (TTP)
TTP is defined as the duration of time from the start of treatment to the first objectively documented instance of progressive disease.
Time frame: Up to 5 years after the last patient stops treatment
Time to treatment failure (TTF)
TTF is defined as the duration of time from start of treatment to discontinuation of study treatment for reasons defined in the protocol.
Time frame: Up to 5 years after the last patient stops treatment
Progression free survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time frame: Up to 5 years after the last patient stops treatment
Clinical benefit rate (CBR)
CBR is defined as the rates of complete response (CR), partial response (PR) and stable disease (SD).
Time frame: Up to 5 years after the last patient stops treatment
Duration of response (DOR)
Per RECIST v1.1, DOR will be assessed by the duration of overall response, duration fo CR/PR, and duration of SD.
Time frame: Up to 5 years after the last patient stops treatment
Correlation of biomarkers related to PD-L1 blockade with objective response rate (ORR), CBR, PFS, OS, and DOR.
Efficacy will be assessed according to tumor PD-L1 expression level and tumor infiltrating lymphocytes PD-L1 expression levels.
Time frame: Up to 5 years after the last patient stops treatment
Efficacy according to hormone receptor status (ER/PR)
This will be a future subset analysis.
Time frame: Up to 5 years after the last patient stops treatment
Feasibility of discontinuation of corticosteroids use after 2 weekly doses of paclitaxel
This will be assessed by CTCAE v4.0.
Time frame: Up to 5 years after the last patient stops treatment
Rate of occurrence of paclitaxel-related infusion hypersensitivity reaction after discontinuation of corticosteroids
This will be assessed by CTCAE v4.0.
Time frame: An average of 18 weeks
Cardiac safety
Quarterly MUGA or ECHO results assessing occurrence of left ventricular dysfunction.
Time frame: An average of 18 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.