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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002113-29 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab | Experimental | Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks. |
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| Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg | Experimental | Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks. |
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| Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg | Experimental | Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks. |
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| Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg | Experimental | Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks. |
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| Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294-3300 | United States | ||
| University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute |
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| Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel | Experimental | Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks. |
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| Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab | Experimental | 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. |
|
| Cohort 2B: Atezolizumab/Trastuzumab emtansine | Experimental | 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. |
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| Cohort 2C: Safety Expansion | Experimental | 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. |
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| Cohort 2D: Safety Expansion | Experimental | 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. |
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| Carboplatin | Drug | 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. |
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| Docetaxel | Drug | Docetaxel 75 mg/m^2 administered via IV infusion on Day 1 every 21-days for 6 cycles. |
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| Pertuzumab | Drug | Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle. |
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| Trastuzumab | Drug | 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. |
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| Trastuzumab emtansine | Drug | 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). |
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| Doxorubicin | Drug | 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. |
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| Cyclophosphamide | Drug | 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. |
|
| 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) |
| 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) |
| 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 |
| 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) |
| 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) |
| 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) |
| 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) |
| Number of Treatment Cycles Received | Baseline up to approximately 3 years |
| Percentage of Participants With Various Dose Intensity | Baseline up to approximately 3 year |
| 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) |
| 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 |
| 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 |
| 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) |
| 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 |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D016190 | Carboplatin |
| D000077143 | Docetaxel |
| C485206 | pertuzumab |
| D000068878 | Trastuzumab |
| D000080044 | Ado-Trastuzumab Emtansine |
| D004317 | Doxorubicin |
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D008453 | Maytansine |
| D018942 | Macrolides |
| D007783 | Lactones |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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