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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

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.

Condition or disease Intervention/treatment Phase
HER2-Positive Metastatic Breast Cancer HER2-Negative Metastatic Breast Cancer Locally Advanced or Early Breast Cancer Drug: Atezolizumab Drug: Carboplatin Drug: Docetaxel Drug: Pertuzumab Drug: Trastuzumab Drug: Trastuzumab emtansine Drug: Doxorubicin Drug: Cyclophosphamide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 98 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 31, 2015
Actual Primary Completion Date : November 13, 2019
Actual Study Completion Date : November 13, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.
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: 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

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.
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: 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

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.
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: 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

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.
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: 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

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.
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: 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.

Experimental: Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel
Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.
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: 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

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.
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

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.
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

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.
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: 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

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.
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: 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




Primary Outcome Measures :
  1. Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F [ Time Frame: Baseline up to Day 21 ]
  2. Percentage of Participants With DLT - Cohort 1E [ Time Frame: Baseline up to Day 28 ]
  3. 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 ]

Secondary Outcome Measures :
  1. 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)

  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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 ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. Number of Treatment Cycles Received [ Time Frame: Baseline up to approximately 3 years ]
  13. Percentage of Participants With Various Dose Intensity [ Time Frame: Baseline up to approximately 3 year ]
  14. 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) ]
  15. 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 ]
  16. 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 ]
  17. 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02605915


Locations
Show Show 20 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02605915    
Other Study ID Numbers: GO29831
2015-002113-29 ( EudraCT Number )
First Posted: November 16, 2015    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Carboplatin
Docetaxel
Doxorubicin
Liposomal doxorubicin
Trastuzumab
Atezolizumab
Pertuzumab
Maytansine
Ado-trastuzumab emtansine
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors