Trial of Nivolumab With Chemotherapy as Neoadjuvant Treatment in Inflammatory Breast Cancer (IBC)

Study Overview
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Brief Summary
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Study of efficacy of nivolumab with neoadjuvant chemotherapy in patients with IBC

Detailed Description
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The purpose of this study is to determine whether the addition of nivolumab to chemotherapy improves pathologic complete response (pCR) in the breast and post-therapy lymph nodes evaluated histologically (ypT0/Tis ypN0) in patients with inflammatory breast cancer (IBC).

Official Title
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Phase II Trial of Nivolumab With Chemotherapy as Neoadjuvant Treatment in Inflammatory Breast Cancer (IBC)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Nivolumab 360mg
* Drug: Paclitaxel 80mg/m^2
* Drug: Doxorubicin 60mg/m^2
* Drug: Cyclophosphamide 600mg/m^2
* Drug: Paclitaxel 80mg/m^2 or Docetaxel 75mg/m^2
* Drug: Trastuzumab 8mg/kg and 6 mg/kg
* Drug: Pertuzumab 840mg and 420mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed inflammatory breast cancer without distant metastases and have not received prior chemotherapy or immunotherapy. All breast cancer subtypes are allowed: Triple negative breast cancer (TNBC); Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative; HR-positive or HR-negative and HER2-positive Exclusion Criteria: Clinical or radiologic evidence of distant metastases Malignancy that progressed within the last five years. Cardiac disease (history of and/or active disease) HIV positive Neuropathy ≥ Grade 2, per the NCI CTCAE v5.0 Allogeneic stem cell or solid organ transplantation Autoimmune disease where in the opinion of the Investigator would preclude the use of immunotherapy Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), or evidence of active pneumonitis Tuberculosis Pregnancy or lactation Treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies Treatment with systemic immunosuppressive medications Cardiopulmonary dysfunction Clinically significant history of liver disease, including cirrhosis, autoimmune hepatic disorders, HIV infection, or active Hepatitis B or Hepatitis C Subject is pregnant or nursing Known hypersensitivity to the components of the study drugs(s)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HER2-negative, including TNBC or HR-positive<br> | Drug: Nivolumab 360mg<br>* Nivolumab 360 mg IV on Day 1 of every 21 day cycle (Cycle 1-4)<br>Drug: Paclitaxel 80mg/m^2<br>* Paclitaxel 80mg/m^2 IV on Day of 1, 8, 15 of every 21 day cycle (Cycle 1-4)<br>Drug: Doxorubicin 60mg/m^2<br>* Doxorubicin 60 mg/m^2 IV on Day 1 of every 14 day cycle (Cycle 5-8)<br>Drug: Cyclophosphamide 600mg/m^2<br>* Cyclophosphamide 600mg/m^2 on Day 1 of every 14 day cycle (Cycle 5-8)<br>|
| Experimental: HER2-positive, independent of HR status<br> | Drug: Nivolumab 360mg<br>* Nivolumab 360 mg IV on Day 1 of every 21 day cycle (Cycle 1-4)<br>Drug: Doxorubicin 60mg/m^2<br>* Doxorubicin 60 mg/m^2 IV on Day 1 of every 14 day cycle (Cycle 5-8)<br>Drug: Cyclophosphamide 600mg/m^2<br>* Cyclophosphamide 600mg/m^2 on Day 1 of every 14 day cycle (Cycle 5-8)<br>Drug: Paclitaxel 80mg/m^2 or Docetaxel 75mg/m^2<br>* Paclitaxel 80mg/m^2 on Day 1, 8, 15 of every 21 day cycle (Cycle 1-4) OR Docetaxel 75mg/m^2 on Day 1 of every 21 day cycle (Cycle 1-4)<br>Drug: Trastuzumab 8mg/kg and 6 mg/kg<br>* Trastuzumab 8mg/kg IV on Day 1 of Cycle 1 and then 6mg/kg IV on Day 1 of Cycle 2-4<br>Drug: Pertuzumab 840mg and 420mg<br>* Pertuzumab 840mg on Day 1 of Cycle 1 and then 420mg IV on Day 1 of Cycle 2-4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Had a Pathological Complete Response (pCR) | pCR is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy (ypT0/Tis ypN0). | up to 16 weeks | 
| Number of Participants Who Had a Pathological Complete Response (pCR) | pCR is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy (ypT0/Tis ypN0). | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nivolumab