Clinical trial NCT02605915: Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
Official title: A Phase Ib, Open-Label Study Evaluating the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Trastuzumab Emtansine or With Trastuzumab and Pertuzumab (With and Without Docetaxel) in Patients With HER2-Positive Breast Cancer and Atezolizumab With Doxorubicin and Cyclophosphamide in HER2-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HER2-Positive Metastatic Breast Cancer
HER2-Negative Metastatic Breast Cancer
Locally Advanced or Early Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-11-16
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase Ib, open-label, two-stage study with two active regimens in each stage designed to evaluate the safety and tolerability of combination treatment with atezolizumab, trastuzumab, and pertuzumab (with and without docetaxel) or atezolizumab and trastuzumab emtansine in participants with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) and locally advanced early breast cancer (EBC), and atezolizumab with doxorubicin and cyclophosphamide in HER2-negative breast cancer.


Eligibility criteria: Inclusion Criteria:

* Histologically documented HER2-positive and HER2-negative (cohort E only) breast cancer
* Metastatic breast cancer that is measurable (Stage 1) or early breast cancer with a primary tumor size greater than (\>) 2 centimeter (cm) (Stage 2)
* Eastern cooperative oncology group (ECOG) performed status of 0, 1 or 2; 0 or 1 (cohort E only)
* Life expectancy of 12 or more weeks
* Adequate hematologic and end-organ function
* Left ventricular ejection fraction greater than or equal to (\>=) 50 percentage (%); \>=55% (cohort E only)

Exclusion Criteria:

* Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
* Leptomeningeal disease
* Pregnancy or lactation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation
* Positive test for human immunodeficiency virus (HIV)
* Active hepatitis B or hepatitis C

Primary outcomes:
measure: Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F
timeFrame: Baseline up to Day 21
measure: Percentage of Participants With DLT - Cohort 1E
timeFrame: Baseline up to Day 28
measure: Percentage of Participants With Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for AEs, Version 4.0 (NCI CTCAE V4.0)
timeFrame: Baseline up to approximately 3 years
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of Atezolizumab
timeFrame: Cohorts 1A, 1B, 1C, 1D, E1, 1F, 2A, 2B, 2C, 2D: pre-infusion (Hour 0), 30 minutes after end of atezolimumab infusion on Day 1 Cycle 1 (cycle length=21 days) up to approximately 3 years (detailed timeframe provided in measure description)
measure: Minimum Serum Concentration (Cmin) of Atezolizumab
timeFrame: pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3 (except cohort 1E), 4, 8 (cycle length=21 days), on Day 1 of every 8 cycles until study treatment/early discontinuation, 120 days after treatment completion/discontinuation (up to approximately 3 years)
measure: Cmin of Trastuzumab
timeFrame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
measure: Cmin of Trastuzumab Emtansine
timeFrame: Cohorts 1B, 1C, 1D, 2B, 2C: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
measure: Cmin of Pertuzumab
timeFrame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
measure: Cmin of Doxorubicin
timeFrame: Cohort 1E: at the end of doxorubicin infusion, 4 and 8 hours after doxorubicin infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days)
measure: Cmin of Cyclophosphamide
timeFrame: Cohort 1E: at the end of cyclophosphamide infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days), 4 and 8 hours after cyclophosphamide infusion on Day 1 of Cycle 1
measure: Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Atezolimumab
timeFrame: pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3 (except cohort 1E), 4, 8 (cycle length=21 days), on Day 1 of every 8 cycles until study treatment/early discontinuation, 120 days after treatment completion/discontinuation (up to approximately 3 years)
measure: Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab
timeFrame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
measure: Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine
timeFrame: Cohorts 1B, 1C, 1D, 2B, 2C: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
measure: Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Pertuzumab
timeFrame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
measure: Number of Treatment Cycles Received
timeFrame: Baseline up to approximately 3 years
measure: Percentage of Participants With Various Dose Intensity
timeFrame: Baseline up to approximately 3 year
measure: Plasma Concentration of Doxorubicin
timeFrame: Cohort 1E: at the end of doxorubicin infusion, 4 and 8 hours after doxorubicin infusion on Day 1 Cycle 1 and 4 (cycle length=21 days)
measure: Plasma Concentration of Cyclophosphamide
timeFrame: Cohort 1E: at the end of cyclophosphamide infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days), 4 and 8 hours after cyclophosphamide infusion on Day of Cycle 1
measure: Plasma Concentration of 4-Hydroxycyclophosphamide
timeFrame: Cohort 1E: at the end of cyclophosphamide infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days), 4 and 8 hours after cyclophosphamide infusion on Day of Cycle 1
measure: Plasma Concentration of Docetaxel
timeFrame: Cohort 1F: at the end of docetaxel infusion, 4 and 8 hours after docetaxel infusion on Day 1 Cycle 1 and 3 (cycle length=21 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute
state: Arkansas
city: Joliet
country: United States
facility: Joliet oncology hematology associates
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Research, Inc.
state: Indiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Center; Department of Oncology
state: Michigan
city: Kansas City
country: United States
facility: HCA Midwest Division
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee Womens Hospital
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street
state: Tennessee
city: Germantown
country: United States
facility: West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center CTRC at UTHSCSA
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: