To date no targeted agents are available to treat TNBC. Therefore chemotherapy is the only treatment option. TNBC often has a high amount of tumour infiltrating lymphocytes. Stimulating the immune cells of TNBC might therefore be an option for these patients to increase the pathological complete response. pCR is highly correlated with outcome in TNBC. Therefore the addition of a checkpoint inhibitor in addition to chemotherapy might be an additional option for these patients.
To date no targeted agents are available to treat TNBC. Therefore chemotherapy is the only treatment option. TNBC often has a high amount of tumour infiltrating lymphocytes. Stimulating the immune cells of TNBC might therefore be an option for these patients to increase the pathological complete response. pCR is highly correlated with outcome in TNBC. Therefore the addition of a checkpoint inhibitor in addition to chemotherapy might be an additional option for these patients. The primary objective therefore is to compare the pathological complete response (pCR= ypT0 ypN0) rates of neoadjuvant treatment of sequential, nab-Paclitaxel followed by EC +/- the PD-L1 antibody MEDI4736 in patients with early triple negative breast cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
174
MEDI4736 1.5g total i.v. every 4 weeks As monotherapy for the first two weeks (0.75g absolute) (part 1) followed by: MEDI4736 in combination with nab-paclitaxel 125 mg/m² every week for 12 weeks (part 2) followed by MEDI4736 in combination with epirubicin 90mg/m² plus cyclophosphamide 600 mg/m² every 2 weeks for 4 cycles (part 3).
Placebo i.v. every 4 weeks As monotherapy for the first two weeks (0.75g absolute) (part 1) followed by: Placebo in combination with nab-paclitaxel 125 mg/m² every week for 12 weeks (part 2) followed by MEDI4736/Placebo in combination with epirubicin 90mg/m² plus cyclophosphamide 600 mg/m² every 2 weeks for 4 cycles (part 3).
nab-Paclitaxel 125 mg/m² weekly for 12 weeks
Centrum für Hämatologie und Onkologie am Bethanien-Krankenhaus
Frankfurt am Main, Hesse, Germany
pathological complete response (pCR= ypT0 ypN0)
To compare the pathological complete response (pCR= ypT0 ypN0) rates of neoadjuvant treatment of sequential, nab-Paclitaxel followed by EC +/- the PD-L1 antibody MEDI4736 in patients with early triple negative breast cancer.
Time frame: 22 weeks
pCR rates per arm
To assess the pCR rates per arm separately for the stratified subpopulations.
Time frame: 22 weeks
Rates of ypT0/is ypN0
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.
Time frame: 22 weeks
Rates of ypT0/is ypN0/+
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.
Time frame: 22 weeks
Rates of ypT(any) ypN0
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.
Time frame: 22 weeks
Rates of ypT0 ypN0/+
To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests (sonography, mammography, or MRI) after treatment in different arms.
Time frame: 22 weeks
Clinical response
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Epirubicin 90 mg/m² 2-weekly for 8 weeks
Cyclophosphamide 600 mg/m² 2-weekly for 8 weeks
To assess clinical response rate after taxane in both groups.
Time frame: 22 weeks
Breast conservation rate
To determine the breast conservation rate after each treatment.
Time frame: 22 weeks
Toxicity and compliance as measured by number of participants with treatment-related
Number of participants with treatment-related adverse events CTCAE v4.0
Time frame: 22 weeks
Molecular markers and gene expression
To examine and compare pre-specified molecular markers and gene expression signatures such as tumor infiltrating lymphocytes, PD-1, PD-L1, Ki-67, etc. on core biopsies before chemotherapy, after the window phase and surgical tissue after end of chemotherapy (in %)
Time frame: 22 weeks
Survival
To determine loco-regional invasive recurrence free survival (LRRFS), distant-disease-free survival (DDFS), invasive disease-free survival (IDFS), event free survival (EFS per FDA definition) and overall survival (OS) in different arms and according to stratified subpopulations (in months)
Time frame: 22 weeks