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

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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).


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
250 Old Hook Road
Westwood, New Jersey 07652
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Baltimore, Maryland 21231
410-955-6190
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins The name Johns Hopkins has become synonymous...
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Baltimore, MD
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345 St Paul Pl
Baltimore, Maryland 21202
(410) 332-9000
Mercy Medical Center "Mercy Medical Center" is a hospital located in Baltimore, Maryland. The landmark...
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Baltimore, MD
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Billings, Montana 59102
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Billings, MT
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Bronx, New York 10461
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Bronx, NY
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Carrollton, Georgia 30117
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Carrollton, GA
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2200 East 3rd Street
Chattanooga, Tennessee 37404
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Chattanooga, TN
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Fort Worth, TX
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Honolulu, Hawaii 96819
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Honolulu, HI
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Kansas City, Missouri 64132
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Kansas City, MO
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Mount Kisco, New York 10549
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Mount Kisco, NY
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250 25th Ave N, Ste 100
Nashville, Tennessee 37023
615-320-5090
Tennessee Oncology, PLLC Since 1976 Tennessee Oncology has been providing quality cancer care. In 2013,...
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Nashville, TN
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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New York, NY
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Norwalk, Connecticut 06856
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Norwalk, CT
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Palo Alto, California 94304
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Palo Alto, CA
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Spokane, Washington 99218
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Spokane, WA
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Tacoma, Washington 98405
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Tacoma, WA
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Waratah, New South Wales 2298
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Waratah,
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