This study that aims to evaluate the addition of MPDL3280A (atezolizumab) to carboplatin and nab-paclitaxel in patients with early high-risk and locally advanced triple negative breast cancer. compared to the control arm of carboplatin and abraxane. Half of participants will receive MPDL3280A in combination with carboplatin and abraxane, while the other half will receive only carboplatin and abraxane.
Emerging evidence shows that many breast cancers with triple negative and basal like features have infiltration by mononuclear cells and lymphocytes. Irrespective of the entity of tumor infiltration by mononuclear cells, expression of immune regulatory checkpoints such as PD-1 and its ligand B7-H1 (or PD-L1) negatively affect the results of treatments. These data suggest that a subset of patients have an ongoing immune response within the tumor micro-environment, and that PD-L1 expression is an adaptive method of tumor resistance to tumor infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, the data suggests a role for immune regulation of response to chemotherapy, and support the concept that blockade of immune check-points may favor the achievement of durable response by immune mechanisms themselves, and in combination with classical chemotherapy. MPDL3280A (atezolizumab) is a human monoclonal antibody containing an engineered Fc-domain to optimize efficacy and safety that targets PD-L1 and blocks binding of its receptors, including PD-1 and B7.1. Based on these considerations, we plan to conduct a study of the combination of abraxane and carboplatin with or without PDL1-directed antibody in women with locally advanced breast cancer suitable for neoadjuvant therapy with the aim to improve event-free survival
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
278
Carboplatin AUC 2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles
Abraxane, 125 mg/m2 will be given i.v. on day 1 and day 8 q 3 weeks for a total of 8 cycles
MPDL3280A, 1200 mg. will be given i.v. infusion on day 1 q 3 weeks for a total of 8 cycles
Event Free Survival (EFS)
To compare EFS (disease progression while on neoadjuvant therapy or disease recurrence after surgery) in the two study arms
Time frame: 5 years after the randomization of the last patient
Pathological complete response (pCR)
Assess the rate of pCR defined as ypT0-ypTis ypN0 at surgery in the two treatment arms
Time frame: At surgery, an expected average of 34 weeks after the randomization of the last patient
Clinical objective response
Assess the clinical response rate after neoadjuvant therapy
Time frame: Participants will be followed for the duration of neoadjuvant therapy, an expected average of 26 weeks
Distant Event Free Survival (DEFS)
To compare the DEFS, defined as the occurrence of distant disease progression while on neoadjuvant therapy or distant recurrence after surgery in the two treatment arms
Time frame: 5 years after the randomization of the last patients
Number of participants with adverse events as a Measure of Safety and Tolerability
Number of participants with Adverse Events and related grade
Time frame: Participants wil be followed for up to 5 years from the last randomized patient
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Breast cancer surgery (breast and axilla) either conservative or radical not later than 6 weeks
AC or EC (adriamycin or epirubicin and cyclophosphamide) or FEC (fluorouracil, epirubicin, and cyclophosphamide) on day 1 every three weeks for 4 cycles to be delivered after surgery
Brustgesundheitzentrum Tirol, Univ. Frauenklinik Innsbruck
Innsbruck, Austria
Universitätsklinik für Innere Medizin III, mit Hämatologie, internistischer Onkologie, Hämostaseologie, Infektiologie, Rheumatologie und Onkologisches Zentrum
Salzburg, Austria
Klinikum Augsburg International Patient Service
Augsburg, Germany
Frauenarzt-Zentrum-Zehlendorf
Berlin, Germany
Augusta-Kranken-Anstalt gGmbH Klinik für Hämatologie, Onkologie & Palliativmedizin
Bochum, Germany
Uniklinik Köln Klinik und Poliklinic für Frauenheilkunde und Geburtshilfe Brestzentrum
Cologne, Germany
Brustzentrum St. Elisabeth-Krankenhaus
Cologne, Germany
Bethanien-Krankenhaus Onkologisches Zentrum
Frankfurt, Germany
Markus Krankenhaus Klinik für Gynäkologie und Geburtshilfe
Frankfurt, Germany
Gynäkologisch-Onkologische Praxis
Hanover, Germany
...and 31 more locations