Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
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
2 other identifiers
interventional
98
1 country
20
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2015
Longer than P75 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 12, 2015
CompletedFirst Posted
Study publicly available on registry
November 16, 2015
CompletedStudy Start
First participant enrolled
December 31, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 13, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 13, 2019
CompletedFebruary 5, 2020
January 1, 2020
3.9 years
November 12, 2015
January 31, 2020
Conditions
Outcome Measures
Primary Outcomes (3)
Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F
Baseline up to Day 21
Percentage of Participants With DLT - Cohort 1E
Baseline up to Day 28
Percentage of Participants With Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for AEs, Version 4.0 (NCI CTCAE V4.0)
Baseline up to approximately 3 years
Secondary Outcomes (17)
Maximum Serum Concentration (Cmax) of Atezolizumab
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)
Minimum Serum Concentration (Cmin) of Atezolizumab
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)
Cmin of Trastuzumab
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)
Cmin of Trastuzumab Emtansine
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)
Cmin of Pertuzumab
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)
- +12 more secondary outcomes
Study Arms (10)
Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
EXPERIMENTALParticipants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.
Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg
EXPERIMENTALParticipants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks.
Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg
EXPERIMENTALParticipants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks.
Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg
EXPERIMENTALParticipants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks.
Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide
EXPERIMENTALParticipants with HER2-negative breast cancer will receive atezolizumab (every 2 weeks) in combination with doxorubicin (every 2 weeks) and cyclophosphamide for four cycles. After the completion of four cycles of combination atezolizumab /doxorubicin / cyclophosphamide, atezolizumab will be continued as a single-agent at a dose of 1200 mg every 3 weeks.
Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel
EXPERIMENTALParticipants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.
Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab
EXPERIMENTALParticipants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks.
Cohort 2B: Atezolizumab/Trastuzumab emtansine
EXPERIMENTALParticipants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks.
Cohort 2C: Safety Expansion
EXPERIMENTALParticipants with HER2-positive metastatic breast cancer/unresectable locally advanced breast cancer who received prior treatment with trastuzumab and a taxane chemotherapy will receive atezolizumab in combination with trastuzumab emtansine at the dose determined from stage 1, every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity.
Cohort 2D: Safety Expansion
EXPERIMENTALParticipants with HER2-positive metastatic breast cancer recently progressed on an HP containing regimen will receive atezolimumab in combination with trastuzumab and pertuzumab every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity.
Interventions
Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.
Carboplatin will be administered at an initial target of area under the curve (AUC) of 6 milligrams per milliliter\*min (mg/mL\*min) via an IV infusion on Day 1 of every 21-days for 6 cycles.
Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.
Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).
Doxorubicin will be administered at 60 mg/m\^2 every 2 weeks as an IV bolus over 3 to 5 minutes or as an infusion over 15 to 30 minutes.
Cyclophosphamide will be administered at 600 mg/m\^2 on Day 1 of each 21 day cycle as an IV bolus over 3 to 5 minutes or as an infusion, in accordance with local policy.
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
University of Alabama at Birmingham
Birmingham, Alabama, 35294-3300, United States
University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute
Little Rock, Arkansas, 72205, United States
Joliet oncology hematology associates
Joliet, Illinois, 60435, United States
Horizon Oncology Research, Inc.
Lafayette, Indiana, 47905, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287, United States
Karmanos Cancer Center; Department of Oncology
Detroit, Michigan, 48201, United States
HCA Midwest Division
Kansas City, Missouri, 64132, United States
Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart
The Bronx, New York, 10461, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Duke Cancer Center
Durham, North Carolina, 27710, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, 45242, United States
St. Luke's University Health Network
Bethlehem, Pennsylvania, 18015, United States
Kimmel Cancer Center Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213, United States
Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street
Chattanooga, Tennessee, 37404, United States
West Clinic
Germantown, Tennessee, 38138, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Cancer Therapy and Research Center CTRC at UTHSCSA
San Antonio, Texas, 78229, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 12, 2015
First Posted
November 16, 2015
Study Start
December 31, 2015
Primary Completion
November 13, 2019
Study Completion
November 13, 2019
Last Updated
February 5, 2020
Record last verified: 2020-01