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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02605915
Recruitment Status : Completed
First Posted : November 16, 2015
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE November 12, 2015
First Posted Date  ICMJE November 16, 2015
Last Update Posted Date February 5, 2020
Actual Study Start Date  ICMJE December 31, 2015
Actual Primary Completion Date November 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
  • Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F [ Time Frame: Baseline up to Day 21 ]
  • Percentage of Participants With DLT - Cohort 1E [ Time Frame: 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) [ Time Frame: Baseline up to approximately 3 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 13, 2015)
  • Number of participants with dose limiting toxicities (DLTs) [ Time Frame: up to Day 21 ]
  • Number of participants with adverse events (AEs) according to national cancer institute common terminology criteria for AEs, version 4.0 (NCI CTCAE v4.0) [ Time Frame: Baseline up to approximately 2 years 9 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2017)
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ 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) ]
    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)
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ 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) ]
  • Cmin of Trastuzumab [ 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) ]
  • Cmin of Trastuzumab Emtansine [ 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) ]
  • Cmin of Pertuzumab [ 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) ]
  • Cmin of Doxorubicin [ 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) ]
  • Cmin of Cyclophosphamide [ 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 ]
  • Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Atezolimumab [ 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) ]
  • Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab [ 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) ]
  • Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine [ 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) ]
  • Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Pertuzumab [ 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) ]
  • Number of Treatment Cycles Received [ Time Frame: Baseline up to approximately 3 years ]
  • Percentage of Participants With Various Dose Intensity [ Time Frame: Baseline up to approximately 3 year ]
  • Plasma Concentration of Doxorubicin [ 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) ]
  • Plasma Concentration of Cyclophosphamide [ 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 ]
  • Plasma Concentration of 4-Hydroxycyclophosphamide [ 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 ]
  • Plasma Concentration of Docetaxel [ 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2015)
  • Number of participants with anti-therapeutic antibody (ATA) response [ Time Frame: Approximately 2 years 9 months ]
  • Number of participants with changes in vital signs, electrocardiogram (ECG) and clinical laboratory results [ Time Frame: Approximately 2 years 9 months ]
  • Number of treatment cycles [ Time Frame: Approximately 2 years 9 months ]
  • Dose intensity [ Time Frame: Approximately 2 years 9 months ]
  • Maximum serum concentration (Cmax) of atezolizumab [ Time Frame: Up to approximately 2 years 9 months ]
  • Minimum serum concentration (Cmin) of atezolizumab [ Time Frame: Up to approximately 2 years 9 months ]
  • Cmin of trastuzumab [ Time Frame: Up to approximately 2 years 9 months ]
  • Cmin of trastuzumab emtansine [ Time Frame: Up to approximately 2 years 9 months ]
  • Cmin of pertuzumab [ Time Frame: Up to approximately 2 years 9 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HER2-Positive Metastatic Breast Cancer
  • HER2-Negative Metastatic Breast Cancer
  • Locally Advanced or Early Breast Cancer
Intervention  ICMJE
  • 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.
    Other Name: Tecentriq, RO5541267
  • Drug: 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.
  • Drug: Docetaxel
    Docetaxel 75 mg/m^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
  • Drug: Pertuzumab
    Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
    Other Name: RO4368451
  • Drug: 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.
    Other Name: RO0452317
  • Drug: 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).
    Other Name: RO5304020
  • Drug: 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.
  • Drug: 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.
Study Arms  ICMJE
  • Experimental: Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
    Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Pertuzumab
    • Drug: Trastuzumab
  • Experimental: Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg
    Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Trastuzumab emtansine
  • Experimental: Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg
    Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Trastuzumab emtansine
  • Experimental: Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg
    Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Trastuzumab emtansine
  • Experimental: Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide
    Participants 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Doxorubicin
    • Drug: Cyclophosphamide
  • Experimental: Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel
    Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Docetaxel
    • Drug: Pertuzumab
    • Drug: Trastuzumab
  • Experimental: Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab
    Participants 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Carboplatin
    • Drug: Docetaxel
    • Drug: Pertuzumab
    • Drug: Trastuzumab
  • Experimental: Cohort 2B: Atezolizumab/Trastuzumab emtansine
    Participants 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Carboplatin
    • Drug: Docetaxel
    • Drug: Pertuzumab
    • Drug: Trastuzumab
    • Drug: Trastuzumab emtansine
  • Experimental: Cohort 2C: Safety Expansion
    Participants 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Trastuzumab emtansine
  • Experimental: Cohort 2D: Safety Expansion
    Participants 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:
    • Drug: Atezolizumab
    • Drug: Pertuzumab
    • Drug: Trastuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: May 16, 2017)
98
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2015)
66
Actual Study Completion Date  ICMJE November 13, 2019
Actual Primary Completion Date November 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02605915
Other Study ID Numbers  ICMJE GO29831
2015-002113-29 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP