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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03197935




Registration number
NCT03197935
Ethics application status
Date submitted
21/06/2017
Date registered
23/06/2017
Date last updated
6/08/2019

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
2016-004734-22
Secondary ID [2] 0 0
WO39392
Universal Trial Number (UTN)
Trial acronym
IMpassion031
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple-negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
Treatment: Drugs - Placebo
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Filgrastim
Treatment: Drugs - Pegfilgrastim

Experimental: Atezolizumab and Chemotherapy - Participants will receive atezolizumab (840 milligrams [mg]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter [mg/m^2]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m^2) and cyclophosphamide (600 mg/m^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will continue to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy.

Placebo Comparator: Placebo and Chemotherapy - Participants will receive placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m^2) and cyclophosphamide (600 mg/m^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed.


Treatment: Drugs: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
Atezolizumab will be administered as per schedule described in respective arm.

Treatment: Drugs: Placebo
Placebo matched to atezolizumab will be administered as per schedule described in respective arm.

Treatment: Drugs: Nab-paclitaxel
Nab-paclitaxel will be administered as per schedule described in the arms.

Treatment: Drugs: Doxorubicin
Doxorubicin will be administered as per schedule described in the arms.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered as per schedule described in the arms.

Treatment: Drugs: Filgrastim
Filgrastim will be administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Treatment: Drugs: Pegfilgrastim
Pegfilgrastim will be administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System
Timepoint [1] 0 0
Week 21
Primary outcome [2] 0 0
Percentage of Participants with pCR in Subpopulation with PD-L1-Positive Tumor Status (tumor-infiltrating immune cell [IC] 1/2/3) Using AJCC Staging System
Timepoint [2] 0 0
Week 21
Secondary outcome [1] 0 0
Event-Free Survival (EFS) in All Participants
Timepoint [1] 0 0
From randomization until documented disease recurrence, progression, or death from any cause (up to approximately 66 months)
Secondary outcome [2] 0 0
Event-Free Survival (EFS) in Subpopulation with PD-L1-Postive Tumor Status
Timepoint [2] 0 0
From randomization until documented disease recurrence, progression, or death from any cause (up to approximately 66 months)
Secondary outcome [3] 0 0
Disease-Free Survival (DFS) in All Participants Who Undergo Surgery
Timepoint [3] 0 0
From surgery until documented disease recurrence or death from any cause (up to approximately 66 months)
Secondary outcome [4] 0 0
Disease-Free Survival (DFS) in Subpopulation of Participants with PD-L1-Positive Tumor Status Who Undergo Surgery
Timepoint [4] 0 0
From surgery until documented disease recurrence or death from any cause (up to approximately 66 months)
Secondary outcome [5] 0 0
Overall survival (OS) in All Participants
Timepoint [5] 0 0
From randomization to the date of death from any cause (up to approximately 66 months)
Secondary outcome [6] 0 0
Overall survival (OS) in Subpopulation with PD-L1-Positive Tumor Status
Timepoint [6] 0 0
From randomization to the date of death from any cause (up to approximately 66 months)
Secondary outcome [7] 0 0
Changes From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score
Timepoint [7] 0 0
Baseline (Cycle 1 Day 1), and on Day 1 of every cycle thereafter (cycle length = 28 days from Cycles 1 to 5, and 21 days from Cycles 6 to 16) (up to approximately 15 months)
Secondary outcome [8] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [8] 0 0
Baseline up to approximately 66 months
Secondary outcome [9] 0 0
Serum Concentration of Atezolizumab
Timepoint [9] 0 0
Pre-infusion (0 hour), 30 minutes post-infusion on Week 1 Day 1; pre-infusion on Day 1 of Weeks 5, 9, 13, 21, 27, 39, 51; at treatment discontinuation (last dose = up to 15 months), 120 days after last dose (infusion length = 60 minutes)
Secondary outcome [10] 0 0
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [10] 0 0
Pre-infusion (0 hour) on Day 1 of Weeks 1, 5, 9, 13, 21, 27, 39, 51; at treatment discontinuation (last dose = up to 15 months), 120 days after last dose (infusion length = 60 minutes)

Eligibility
Key inclusion criteria
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

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods, and agreement to refrain from
donating eggs

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm

- Women who are not postmenopausal or have undergone a sterilization procedure must have
a negative serum pregnancy test result within 14 days prior to initiation of study
drug
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

- History of cerebrovascular accident within 12 months prior to randomization

- Pregnant or lactating, or intending to become pregnant during the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle; Medical Oncology - Waratah
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit - Bull Creek
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
6149 - Bull Creek
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Hawaii
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Montana
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Belgium
State/province [14] 0 0
Bruxelles
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Belgium
State/province [16] 0 0
Namur
Country [17] 0 0
Belgium
State/province [17] 0 0
Wilrijk
Country [18] 0 0
Brazil
State/province [18] 0 0
BA
Country [19] 0 0
Brazil
State/province [19] 0 0
GO
Country [20] 0 0
Brazil
State/province [20] 0 0
MG
Country [21] 0 0
Brazil
State/province [21] 0 0
PR
Country [22] 0 0
Brazil
State/province [22] 0 0
RJ
Country [23] 0 0
Brazil
State/province [23] 0 0
RS
Country [24] 0 0
Brazil
State/province [24] 0 0
SC
Country [25] 0 0
Brazil
State/province [25] 0 0
SP
Country [26] 0 0
Canada
State/province [26] 0 0
Alberta
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
Canada
State/province [28] 0 0
Quebec
Country [29] 0 0
Germany
State/province [29] 0 0
Bad Nauheim
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Bielefeld
Country [32] 0 0
Germany
State/province [32] 0 0
Düsseldorf
Country [33] 0 0
Germany
State/province [33] 0 0
Gelsenkirchen
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Germany
State/province [35] 0 0
Hannover
Country [36] 0 0
Germany
State/province [36] 0 0
Langen
Country [37] 0 0
Germany
State/province [37] 0 0
Leipzig
Country [38] 0 0
Germany
State/province [38] 0 0
München
Country [39] 0 0
Germany
State/province [39] 0 0
Münster
Country [40] 0 0
Germany
State/province [40] 0 0
Oldenburg
Country [41] 0 0
Italy
State/province [41] 0 0
Lombardia
Country [42] 0 0
Italy
State/province [42] 0 0
Veneto
Country [43] 0 0
Japan
State/province [43] 0 0
Aichi
Country [44] 0 0
Japan
State/province [44] 0 0
Ehime
Country [45] 0 0
Japan
State/province [45] 0 0
Fukushima
Country [46] 0 0
Japan
State/province [46] 0 0
Hiroshima
Country [47] 0 0
Japan
State/province [47] 0 0
Kanagawa
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Saitama
Country [50] 0 0
Japan
State/province [50] 0 0
Tokyo
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Gyeonggi-do
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Seoul
Country [53] 0 0
Poland
State/province [53] 0 0
Warszawa
Country [54] 0 0
Poland
State/province [54] 0 0
Wroclaw
Country [55] 0 0
Poland
State/province [55] 0 0
Lódz
Country [56] 0 0
Spain
State/province [56] 0 0
Cordoba
Country [57] 0 0
Spain
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LA Coruña
Country [58] 0 0
Spain
State/province [58] 0 0
Barcelona
Country [59] 0 0
Spain
State/province [59] 0 0
Madrid
Country [60] 0 0
Spain
State/province [60] 0 0
Sevilla
Country [61] 0 0
Taiwan
State/province [61] 0 0
Taipei
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taoyuan
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Leicester
Country [64] 0 0
United Kingdom
State/province [64] 0 0
London
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Newcastle upon Tyne
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Northwood

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03197935
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: WO39392 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03197935