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

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

Study of efficacy of nivolumab with neoadjuvant chemotherapy in patients with IBC

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: 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

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Bloomington, Indiana, United States, 47405
      • Indiana University
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Maryann Kwa, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Actual): June 12, 2023
• Study Completion (Actual): June 12, 2023

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Inflammatory Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immune Checkpoint Inhibitors; Docetaxel; Cyclophosphamide; Paclitaxel; Trastuzumab; Nivolumab; Albumin-Bound Paclitaxel; Doxorubicin; Pertuzumab
• Other Study ID Numbers: 17-00890

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared.
• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: Data will be available as specified in publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No