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HER2-Positive Metastatic Breast CancerPhase 1NCT02605915

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

A Phase 1 study testing Atezolizumab, Carboplatin and Docetaxel in people with HER2-Positive Metastatic Breast Cancer and HER2-Negative Metastatic Breast Cancer, run by Hoffmann-La Roche at 20 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Carboplatin and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
20 sitesUnited States
Study dates
31 Dec 2015to 13 Nov 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United States20 sites

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • St. Luke's University Health Network

    Bethlehem, Pennsylvania, 18015

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-3300

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street

    Chattanooga, Tennessee, 37404

  • Oncology Hematology Care Inc

    Cincinnati, Ohio, 45242

  • Karmanos Cancer Center; Department of Oncology

    Detroit, Michigan, 48201

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • West Clinic

    Germantown, Tennessee, 38138

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Joliet oncology hematology associates

    Joliet, Illinois, 60435

  • HCA Midwest Division

    Kansas City, Missouri, 64132

  • Horizon Oncology Research, Inc.

    Lafayette, Indiana, 47905

  • University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute

    Little Rock, Arkansas, 72205

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Kimmel Cancer Center Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • Cancer Therapy and Research Center CTRC at UTHSCSA

    San Antonio, Texas, 78229

  • Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart

    The Bronx, New York, 10461

Other trials in United States

About this study

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

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.

Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq, RO5541267

    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.

  • CarboplatinDrug

    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.

  • DocetaxelDrug

    Docetaxel 75 mg/m^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.

  • PertuzumabDrug

    Also called RO4368451

    Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.

  • TrastuzumabDrug

    Also called RO0452317

    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 emtansineDrug

    Also called RO5304020

    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).

  • DoxorubicinDrug

    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.

  • CyclophosphamideDrug

    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 groups in NCT02605915
Study groupRoleWhat they receive
Cohort 1A: Atezolizumab/Trastuzumab/PertuzumabExperimentalParticipants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.
Receives: Drug: Atezolizumab; Drug: Pertuzumab; Drug: Trastuzumab
Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mgExperimentalParticipants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks.
Receives: Drug: Atezolizumab; Drug: 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.
Receives: Drug: Atezolizumab; Drug: 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.
Receives: Drug: Atezolizumab; Drug: 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.
Receives: Drug: Atezolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide
Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ DocetaxelExperimentalParticipants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.
Receives: Drug: Atezolizumab; Drug: Docetaxel; Drug: Pertuzumab; Drug: 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.
Receives: Drug: Atezolizumab; Drug: Carboplatin; Drug: Docetaxel; Drug: Pertuzumab; Drug: 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.
Receives: Drug: Atezolizumab; Drug: Carboplatin; Drug: Docetaxel; Drug: Pertuzumab; Drug: Trastuzumab; Drug: 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.
Receives: Drug: Atezolizumab; Drug: 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.
Receives: Drug: Atezolizumab; Drug: Pertuzumab; Drug: Trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F

    Measured: Baseline up to Day 21

  2. Percentage of Participants With DLT - Cohort 1E

    Measured: 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)

    Measured: Baseline up to approximately 3 years

Secondary outcomes (17)

  1. 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)

    Measured: 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)

  2. Minimum Serum Concentration (Cmin) of Atezolizumab

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: Baseline up to approximately 3 years

  13. Percentage of Participants With Various Dose Intensity

    Measured: Baseline up to approximately 3 year

  14. Plasma Concentration of Doxorubicin

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2015 (estimated)
  2. Study start31 Dec 2015
  3. Primary completion13 Nov 2019
  4. Study completion13 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
98 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02605915
Sponsor's protocol ID
GO29831
Other IDs
2015-002113-29, 2015
Status last verified
Jan 2020
First submitted
12 Nov 2015
Last updated
5 Feb 2020
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab, Carboplatin and Docetaxel in people with HER2-Positive Metastatic Breast Cancer and HER2-Negative Metastatic Breast Cancer, run by Hoffmann-La Roche at 20 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F (time frame: Baseline up to Day 21). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02605915.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.

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