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.
Brief Title
Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
Categories
Completion Date
Completion Date Type
Actual
Conditions
HER2-Positive Metastatic Breast Cancer
HER2-Negative Metastatic Breast Cancer
Locally Advanced or Early 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
* 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
Inclusion 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)
* 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)
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02605915
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
GO29831
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Measure
Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F
Outcome Time Frame
Baseline up to Day 21
Outcome Measure
Percentage of Participants With DLT - Cohort 1E
Outcome Time Frame
Baseline up to Day 28
Outcome 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)
Outcome Time Frame
Baseline up to approximately 3 years
Secondary Ids
Secondary Id
2015-002113-29
Secondary Outcomes
Outcome Description
Cohorts 1A, 1B, 1C, 1D, E1, 1F, 2A, 2B, 2C, 2D: 30 minutes after end of infusion on Day 1 Cycle 1 (cycle length=21 days); pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3 (except cohort 1E), 4, 8, on Day 1 of every 8 cycles until study treatment/early discontinuation, 120 days after treatment completion/discontinuation (up to approximately 3 years)
Outcome Time Frame
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)
Outcome Measure
Maximum Serum Concentration (Cmax) of Atezolizumab
Outcome Time Frame
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)
Outcome Measure
Minimum Serum Concentration (Cmin) of Atezolizumab
Outcome Time Frame
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)
Outcome Measure
Cmin of Trastuzumab
Outcome Time Frame
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)
Outcome Measure
Cmin of Trastuzumab Emtansine
Outcome Time Frame
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)
Outcome Measure
Cmin of Pertuzumab
Outcome Time Frame
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)
Outcome Measure
Cmin of Doxorubicin
Outcome Time Frame
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
Outcome Measure
Cmin of Cyclophosphamide
Outcome Time Frame
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)
Outcome Measure
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Atezolimumab
Outcome Time Frame
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)
Outcome Measure
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab
Outcome Time Frame
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)
Outcome Measure
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine
Outcome Time Frame
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)
Outcome Measure
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Pertuzumab
Outcome Time Frame
Baseline up to approximately 3 years
Outcome Measure
Number of Treatment Cycles Received
Outcome Time Frame
Baseline up to approximately 3 year
Outcome Measure
Percentage of Participants With Various Dose Intensity
Outcome Time Frame
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)
Outcome Measure
Plasma Concentration of Doxorubicin
Outcome Time Frame
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
Outcome Measure
Plasma Concentration of Cyclophosphamide
Outcome Time Frame
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
Outcome Measure
Plasma Concentration of 4-Hydroxycyclophosphamide
Outcome Time Frame
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)
Outcome Measure
Plasma Concentration of Docetaxel
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sun Young Oh
Investigator Email
suyoung@montefiore.org
Investigator Phone
918-405-8404