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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02924883




Registration number
NCT02924883
Ethics application status
Date submitted
21/09/2016
Date registered
5/10/2016
Date last updated
17/02/2021

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer (BC) Who Received Prior Trastuzumab and Taxane Based Therapy
Scientific title
A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab and Taxane Based Therapy
Secondary ID [1] 0 0
2015-004189-27
Secondary ID [2] 0 0
WO30085
Universal Trial Number (UTN)
Trial acronym
KATE2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic 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
Treatment: Drugs - Trastuzumab emtansine
Other interventions - Placebo

Experimental: Trastuzumab Emtansine + Atezolizumab - Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion or matching Placebo followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (approximately 29 months)

Active comparator: Trastuzumab Emtansine + Placebo - Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (approximately 29 months)


Treatment: Drugs: Atezolizumab
Atezolizumab 1200 mg IV infusion

Treatment: Drugs: Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg IV infusion

Other interventions: Placebo
Placebo matched to atezolizumab

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
Timepoint [1] 0 0
Baseline up to approximately 15 months
Primary outcome [2] 0 0
Percentage of Participants With Adverse Events
Timepoint [2] 0 0
Baseline up to study completion, approximately 40 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Baseline up to study completion or death, whichever occurs first, approximately 40 months
Secondary outcome [2] 0 0
Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1
Timepoint [2] 0 0
Baseline up to approximately 15 months
Secondary outcome [3] 0 0
Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1
Timepoint [3] 0 0
Baseline up to approximately 15 months
Secondary outcome [4] 0 0
Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine
Timepoint [4] 0 0
Pre-infusion (0 hour [h]), 30 minutes (min) after end of infusion (EOI) (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days); at any time during study treatment/early discontinuation visit (approx. 40 months)
Secondary outcome [5] 0 0
Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)
Timepoint [5] 0 0
Pre-infusion (0 h) on Day 1 Cycle 1 and 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4 (each cycle = 21 days)
Secondary outcome [6] 0 0
Cmax of Total Trastuzumab
Timepoint [6] 0 0
Pre-infusion (0 h), 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days)
Secondary outcome [7] 0 0
Cmax of Atezolizumab
Timepoint [7] 0 0
Pre-infusion (0 h), 30 min after EOI (over 60 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycles 2, 3, 8, and every 8 cycles thereafter (each cycle=21 days) up to 120 days after treatment completion/early discontinuation (approx. 40 months)
Secondary outcome [8] 0 0
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab
Timepoint [8] 0 0
Pre-infusion (0 h) on Day 1 Cycles 1, 2, 3, 4, 8, and every 8 cycles thereafter (each cycle = 21 days) up to 120 days after treatment completion or early discontinuation (approximately 40 months)
Secondary outcome [9] 0 0
Percentage of Participants With ATAs to Trastuzumab Emtansine
Timepoint [9] 0 0
Pre-infusion (0 h) on Day 1 Cycles 1 and 4 (each cycle = 21 days); and at any time during study treatment/early discontinuation visit (approximately 40 months)

Eligibility
Key inclusion criteria
* Archival tumor samples must be obtained from primary and/or metastatic sites
* Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression
* HER-2 positive BC as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of greater than or equal to (>=) 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies
* Histologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic BC
* Prior treatment for BC in the: adjuvant; unresectable locally advanced; or metastatic settings; which must include both, a taxane and trastuzumab (alone or in combination with another agent)
* Progression must have occurred during or after most recent treatment for locally advanced/metastatic BC or within 6 months after completing adjuvant therapy
* Participants must have measurable disease that is evaluable as per RECIST v1.1
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and for women less than 12 months after the onset of menopause
* Use of highly effective method of contraception as defined by the protocol
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with trastuzumab emtansine, cluster of differentiation 137 agonists, anti-programmed death-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
* Receipt of any anti-cancer drug/biologic or investigational treatment within 21 days prior to Cycle 1 Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1 Day 1; recovery of treatment related toxicity consistent with other eligibility criteria
* Radiation therapy within 2 weeks prior to Cycle 1, Day 1
* History of exposure to the cumulative doses of anthracyclines
* History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or participants who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence
* Cardiopulmonary dysfunction, symptomatic pleural effusion, pericardial effusion, or ascites
* Participants with severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* Current severe, uncontrolled systemic disease
* Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
* Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
* Need for current chronic corticosteroid therapy (>=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids)
* Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than (>) 2 weeks prior to randomization
* Participants with known central nervous system disease
* Leptomeningeal disease
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation
* Active tuberculosis
* Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study
* Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial
* Participants who are breastfeeding, 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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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,QLD,VIC,WA
Recruitment hospital [1] 0 0
St George Hospital; Cancer Care Centre - Kogarah
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology - Woolloongabba
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Center - East Melbourne
Recruitment hospital [5] 0 0
Peninsula and South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [6] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [7] 0 0
St John of God Hospital; Bendat Cancer Centre - Subiaco
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3002 - East Melbourne
Recruitment postcode(s) [5] 0 0
3199 - Frankston
Recruitment postcode(s) [6] 0 0
3021 - St Albans
Recruitment postcode(s) [7] 0 0
6008 - Subiaco
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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
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
New Mexico
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
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
Washington
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Essen
Country [17] 0 0
Germany
State/province [17] 0 0
Freiburg
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Germany
State/province [19] 0 0
Koblenz
Country [20] 0 0
Italy
State/province [20] 0 0
Campania
Country [21] 0 0
Italy
State/province [21] 0 0
Emilia-Romagna
Country [22] 0 0
Italy
State/province [22] 0 0
Friuli-Venezia Giulia
Country [23] 0 0
Italy
State/province [23] 0 0
Sicilia
Country [24] 0 0
Italy
State/province [24] 0 0
Toscana
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Goyang-si
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Spain
State/province [27] 0 0
Cordoba
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
La Coruña
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia
Country [32] 0 0
Taiwan
State/province [32] 0 0
Changhua
Country [33] 0 0
Taiwan
State/province [33] 0 0
Kaohsiung
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taichung
Country [35] 0 0
Taiwan
State/province [35] 0 0
Tainan
Country [36] 0 0
Taiwan
State/province [36] 0 0
Taipei City
Country [37] 0 0
Taiwan
State/province [37] 0 0
Taipei
Country [38] 0 0
Taiwan
State/province [38] 0 0
Taoyuan
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Bath
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Glasgow
Country [41] 0 0
United Kingdom
State/province [41] 0 0
London
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Manchester
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Nottingham
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Sheffield
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Sutton
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Swansea

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.