Clinical Trials /

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

NCT02605915

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
  • 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 IDs

  • ORG STUDY ID: GO29831
  • SECONDARY ID: 2015-002113-29
  • NCT ID: NCT02605915

Conditions

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

Interventions

DrugSynonymsArms
AtezolizumabTecentriq, RO5541267Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
CarboplatinCohort 2A: Atezolizumab/Trastuzumab/Pertuzumab
DocetaxelCohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel
PertuzumabRO4368451Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
TrastuzumabRO0452317Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
Trastuzumab emtansineRO5304020Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg
DoxorubicinCohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide
CyclophosphamideCohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide

Purpose

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 Arms

NameTypeDescriptionInterventions
Cohort 1A: Atezolizumab/Trastuzumab/PertuzumabExperimentalParticipants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.
  • Atezolizumab
  • Pertuzumab
  • Trastuzumab
Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mgExperimentalParticipants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks.
  • Atezolizumab
  • Trastuzumab emtansine
Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mgExperimentalParticipants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks.
  • Atezolizumab
  • Trastuzumab emtansine
Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mgExperimentalParticipants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks.
  • Atezolizumab
  • Trastuzumab emtansine
Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamideExperimentalParticipants 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.
  • Atezolizumab
  • Doxorubicin
  • Cyclophosphamide
Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ DocetaxelExperimentalParticipants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.
  • Atezolizumab
  • Docetaxel
  • Pertuzumab
  • Trastuzumab
Cohort 2A: Atezolizumab/Trastuzumab/PertuzumabExperimentalParticipants 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.
  • Atezolizumab
  • Carboplatin
  • Docetaxel
  • Pertuzumab
  • Trastuzumab
Cohort 2B: Atezolizumab/Trastuzumab emtansineExperimentalParticipants 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.
  • Atezolizumab
  • Carboplatin
  • Docetaxel
  • Pertuzumab
  • Trastuzumab
  • Trastuzumab emtansine
Cohort 2C: Safety ExpansionExperimentalParticipants 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.
  • Atezolizumab
  • Trastuzumab emtansine
Cohort 2D: Safety ExpansionExperimentalParticipants 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.
  • Atezolizumab
  • Pertuzumab
  • Trastuzumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F
Time Frame:Baseline up to Day 21
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
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)
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Number of Treatment Cycles Received
Time Frame:Baseline up to approximately 3 years
Safety Issue:
Description:
Measure:Percentage of Participants With Various Dose Intensity
Time Frame:Baseline up to approximately 3 year
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

August 1, 2017