A Study to Investigate Atezolizumab and Chemotherapy Compared With Placebo and Chemotherapy in the Neoadjuvant Setting in Participants With Early Stage Triple Negative Breast Cancer
Status: | Active, not recruiting |
---|---|
Conditions: | Breast Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 1/31/2019 |
Start Date: | July 24, 2017 |
End Date: | September 26, 2021 |
A Phase III Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Neoadjuvant Anthracycline/Nab-Paclitaxel-Based Chemotherapy Compared With Placebo and Chemotherapy in Patients With Primary Invasive Triple-Negative Breast Cancer
This is a global Phase III, double-blind, randomized, placebo-controlled study designed to
evaluate the efficacy and safety of neoadjuvant treatment with atezolizumab (anti-programmed
death-ligand 1 [anti-PD-L1] antibody) and nab-paclitaxel followed by doxorubicin and
cyclophosphamide (nab-pac-AC), or placebo and nab-pac−AC in participants eligible for surgery
with initial clinically assessed triple-negative breast cancer (TNBC).
evaluate the efficacy and safety of neoadjuvant treatment with atezolizumab (anti-programmed
death-ligand 1 [anti-PD-L1] antibody) and nab-paclitaxel followed by doxorubicin and
cyclophosphamide (nab-pac-AC), or placebo and nab-pac−AC in participants eligible for surgery
with initial clinically assessed triple-negative breast cancer (TNBC).
Inclusion criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically documented TNBC (negative human epidermal growth factor receptor 2
[HER2], estrogen receptor [ER], and progesterone receptor [PgR] status)
- Confirmed tumor programmed death−ligand 1 (PD-L1) evaluation as documented through
central testing of a representative tumor tissue specimen
- Primary breast tumor size of greater than (>) 2 centimeters (cm) by at least one
radiographic or clinical measurement
- Stage at presentation: cT2-cT4, cN0-cN3, cM0
- Participant agreement to undergo appropriate surgical management including axillary
lymph node surgery and partial or total mastectomy after completion of neoadjuvant
treatment
- Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>=) 53
percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
scans
- Adequate hematologic and end-organ function
- Representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in paraffin
blocks (preferred) or at least 20 unstained slides, with an associated pathology
report documenting ER, PgR, and HER2 negativity
Exclusion criteria:
- Prior history of invasive breast cancer
- Stage 4 (metastatic) breast cancer
- Prior systemic therapy for treatment and prevention of breast cancer
- Previous therapy with anthracyclines or taxanes for any malignancy
- History of ductal carcinoma in situ (DCIS), except for participants treated
exclusively with mastectomy >5 years prior to diagnosis of current breast cancer
- History of pleomorphic lobular carcinoma in situ (LCIS), except for participants
surgically managed >5 years prior to diagnosis of current breast cancer
- Bilateral breast cancer
- Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph
nodes
- Axillary lymph node dissection prior to initiation of neoadjuvant therapy
- History of other malignancy within 5 years prior to screening, with the exception of
those with a negligible risk of metastasis or death
- Cardiopulmonary dysfunction
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
- Known allergy or hypersensitivity to the components of the formulations of
atezolizumab, nab-paclitaxel, cyclophosphamide, or doxorubicin, filgrastim or
pegfilgrastim
- Active or history of autoimmune disease or immune deficiency diseases except history
of autoimmune-related hypothyroidism, controlled Type 1 diabetes mellitus, and
dermatologic manifestations of eczema, psoriasis, lichen simplex chronicus, or
vitiligo (e.g., participants with psoriatic arthritis are excluded)
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation
field (fibrosis) is permitted
- Positive human immunodeficiency virus (HIV) test at screening
- Active hepatitis B and hepatitis C virus infection
- Active tuberculosis
- Severe infections within 4 weeks prior to initiation of study treatment, including but
not limited to hospitalization for complications of infection, bacteremia, or severe
pneumonia
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment, except prophylactic antibiotics
- Major surgical procedure within 4 weeks prior to initiation of study treatment or
anticipation of need for a major surgical procedure during the course of the study
- Prior allogeneic stem cell or solid organ transplantation
- Administration of a live attenuated vaccine within 4 weeks prior to initiation of
study treatment or anticipation of need for such a vaccine during the study
- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the participant at high risk from treatment
complications
- Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
checkpoint-blockade therapies, including anti-cluster of differentiation 40
(anti-CD40), anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4),
anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the
drug, whichever is longer, prior to initiation of study treatment
- Treatment with systemic immunosuppressive medications within 2 weeks prior to
initiation of study treatment or anticipation of need for systemic immunosuppressive
medications during the study
We found this trial at
19
sites
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins The name Johns Hopkins has become synonymous...
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Mercy Medical Center "Mercy Medical Center" is a hospital located in Baltimore, Maryland. The landmark...
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2200 East 3rd Street
Chattanooga, Tennessee 37404
Chattanooga, Tennessee 37404
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Tennessee Oncology, PLLC Since 1976 Tennessee Oncology has been providing quality cancer care. In 2013,...
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Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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