Summary
(Protocol #S2206 - Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer) This phase III trial compares the addition of an immunotherapy drug (durvalumab) to usual chemotherapy versus usual chemotherapy alone in treating patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, doxorubicin, and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. There is some evidence from previous clinical trials that people who have a MammaPrint High 2 Risk result may be more likely to respond to chemotherapy and immunotherapy. Adding durvalumab to usual chemotherapy may be able to prevent the cancer from returning for patients with MP2 stage II-III hormone receptor positive, HER2 negative breast cancer.
Description
This study is comparing the usual treatment alone to MEDI4736 (durvalumab) given together with the usual treatment. The addition of MEDI4736 (durvalumab) to the usual treatment could prevent the cancer from returning. But, it could also cause side effects.
This study will help the study doctors find out if this different approach is better, the same, or worse than the usual approach. To decide if it is better, the study doctors will be looking to see if the study drug extends the life of patients and/or prevents the tumor from coming back as compared to the usual approach.
OUTLINE:
STEP 1: Patients without a known MP2 score undergo MammaPrint testing on a previously-collected tissue sample. Patients with MP2 score proceed to STEP 2.
STEP 2: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive paclitaxel intravenously (IV) on days 1 and 8 of each cycle. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
ARM 2: Patients receive paclitaxel IV on days 1 and 8 of each cycle and durvalumab IV over 60 minutes on day 1 of cycles 1, 3, and 5. Treatment repeats every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin IV and cyclophosphamide IV on day 1 of each cycle, and durvalumab IV over 60 minutes on day 1 of cycles 7 and 9. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
All patients also undergo mammography during screening (STEP 1). Patients have the option to also undergo collection of tumor tissue during initial biopsy (STEP 1) and at standard of care (SOC) surgery and undergo collection of blood samples throughout the study.