Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer

HER2-Positive Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02605915
• Other study ID #: GO29831
• Secondary ID: 2015-002113-29
• Status: Completed
• Phase: Phase 1
• Start date: December 31, 2015
• Est. completion date: November 13, 2019

Study information

• Verified date: January 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: November 13, 2019
• Est. primary completion date: November 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-Negative Metastatic Breast Cancer
• HER2-Positive Metastatic Breast Cancer
• Locally Advanced or Early Breast Cancer

Intervention

Drug:
• Atezolizumab
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
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
Docetaxel 75 mg/m^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
• Pertuzumab
Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
• Trastuzumab
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
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
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
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.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart	Bronx	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street	Chattanooga	Tennessee
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Karmanos Cancer Center; Department of Oncology	Detroit	Michigan
United States	Duke Cancer Center	Durham	North Carolina
United States	West Clinic	Germantown	Tennessee
United States	MD Anderson Cancer Center	Houston	Texas
United States	Joliet oncology hematology associates	Joliet	Illinois
United States	HCA Midwest Division	Kansas City	Missouri
United States	Horizon Oncology Research, Inc.	Lafayette	Indiana
United States	University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute	Little Rock	Arkansas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tennessee Oncology	Nashville	Tennessee
United States	Kimmel Cancer Center Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Cancer Therapy and Research Center CTRC at UTHSCSA	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F		Baseline up to Day 21
Primary	Percentage of Participants With DLT - Cohort 1E		Baseline up to Day 28
Primary	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	Maximum Serum Concentration (Cmax) of Atezolizumab	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)	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Cmin of Doxorubicin		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)
Secondary	Cmin of Cyclophosphamide		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
Secondary	Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Atezolimumab		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)
Secondary	Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to 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)
Secondary	Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to 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)
Secondary	Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to 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)
Secondary	Number of Treatment Cycles Received		Baseline up to approximately 3 years
Secondary	Percentage of Participants With Various Dose Intensity		Baseline up to approximately 3 year
Secondary	Plasma Concentration of Doxorubicin		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)
Secondary	Plasma Concentration of Cyclophosphamide		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
Secondary	Plasma Concentration of 4-Hydroxycyclophosphamide		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
Secondary	Plasma Concentration of Docetaxel		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)