Testing the Drug Atezolizumab or Placebo With Usual Therapy in First-Line HER2-Positive Metastatic Breast Cancer
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ClinicalTrials.gov Identifier: NCT03199885 |
Recruitment Status :
Active, not recruiting
First Posted : June 27, 2017
Last Update Posted : August 8, 2022
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Tracking Information | |||||||
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First Submitted Date ICMJE | June 26, 2017 | ||||||
First Posted Date ICMJE | June 27, 2017 | ||||||
Last Update Posted Date | August 8, 2022 | ||||||
Actual Study Start Date ICMJE | March 12, 2019 | ||||||
Estimated Primary Completion Date | January 31, 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Progression free survival [ Time Frame: The time from randomization to the first documented progressive disease assessed up to 7 years ] Will be determined using the current Response Evaluation Criteria in Solid Tumors 1.1 criteria. Analysis will be based on the intent to treat population. The stratified log-rank test will be used to compare the progression free survival between the two treatment arms with the following stratification factors: prior neoadjuvant or adjuvant therapy with trastuzumab (no; yes), estrogen receptor status (positive; negative), disease sites (any visceral without brain metastasis; non-visceral only without brain metastasis; brain metastasis), and choice of taxane (paclitaxel; docetaxel). The Kaplan-Meier estimates will be calculated by treatment arms. Stratified Cox proportional hazards models to estimate the hazard ratio.
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Original Primary Outcome Measures ICMJE |
Progression free survival [ Time Frame: The time from randomization to the first documented progressive disease assessed up to 5 years ] Will be determined using the current Response Evaluation Criteria in Solid Tumors 1.1 criteria. Analysis will be based on the intent to treat population. The stratified log-rank test will be used to compare the progression free survival between the two treatment arms with the following stratification factors: prior neoadjuvant or adjuvant therapy with trastuzumab (no prior trastuzumab; prior trastuzumab and no pertuzumab; prior trastuzumab and pertuzumab), estrogen receptor status (positive; negative), and disease sites (any visceral without brain metastasis; non-visceral only without brain me
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Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Testing the Drug Atezolizumab or Placebo With Usual Therapy in First-Line HER2-Positive Metastatic Breast Cancer | ||||||
Official Title ICMJE | A Randomized, Double-Blind, Phase III Trial of Taxane/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer | ||||||
Brief Summary | This randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab works in treating patients with breast cancer that has spread to other parts of the body (metastatic). Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may interfere with the ability of cancer cells to grow and spread. Immunotherapy with monoclonal antibodies, such as atezolizumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill more tumor cells. *NOTE: This study has a central confirmation step. The purpose of this step is to confirm by central testing that the patient's tumor has specific receptors. If the patient meets all the study requirements, the patient will join the study and begin therapy for breast cancer while the tumor is being tested. |
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Detailed Description | PRIMARY OBJECTIVE: I. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve the progression-free survival (PFS), assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, relative to the addition of a placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) in patients with newly documented HER2-positive measurable metastatic breast cancer. SECONDARY OBJECTIVES: I. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve the overall survival (OS) relative to the addition of placebo to a regimen of pertuzumab and trastuzumab, combined with a taxane (paclitaxel or docetaxel). II. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve the overall objective response (OR), assessed by investigator using RECIST 1.1 criteria, relative to the addition of placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). III. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve PFS, OR, and/or duration of objective response assessed by retrospective blinded central review using RECIST 1.1 criteria, relative to the addition of placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). IV. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will decrease the incidence of subsequent brain metastases in patients without known brain metastases at study entry relative to the addition of placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). V. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will contribute to increased patient-reported fatigue in comparison to the addition of placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). VI. To determine the utility of PD-L1 immunohistochemistry (IHC) staining as a predictive and prognostic biomarker associated with clinical response, as assessed by investigator using RECIST 1.1 criteria, to atezolizumab in combination with trastuzumab and pertuzumab combined with a taxane (paclitaxel or docetaxel). VII. To determine the immune-related toxicity profile of the two treatment regimens. VIII. To determine the cardiac safety profile of the two treatment regimens. EXPLORATORY OBJECTIVES: I. To determine whether the addition of atezolizumab to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel) will improve the progression-free survival and overall objective response, assessed by investigator using immune-modified RECIST (iRECIST) criteria, relative to the addition of a placebo to a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). II. To identify potential biomarkers that can predict benefit from the addition of atezolizumab in patients with newly documented HER2-positive measurable metastatic breast cancer treated with a regimen of pertuzumab and trastuzumab combined with a taxane (paclitaxel or docetaxel). III. To explore the toxicity profile of the two treatment regimens using patient-reported symptomatic adverse events in addition to standard adverse event reports. IV. To determine the feasibility and added value of frequent assessment of toxicity using Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) with electronic(e)PRO reporting. OUTLINE: STEP 1: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. STEP 2: Patients are randomized to 1 of 2 arms. ARM I: Patients receive pertuzumab IV over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36 or docetaxel IV over 60 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive atezolizumab IV over 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive pertuzumab, trastuzumab, and paclitaxel or docetaxel as in Arm I. Patients also receive placebo IV 30-60 minutes on day 22 of cycle 1 and days 1 and 22 of subsequent cycles. Cycles repeat every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for 4 years. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 3 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||
Estimated Enrollment ICMJE |
600 | ||||||
Original Estimated Enrollment ICMJE |
480 | ||||||
Estimated Study Completion Date ICMJE | January 31, 2023 | ||||||
Estimated Primary Completion Date | January 31, 2023 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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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 | Canada, United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03199885 | ||||||
Other Study ID Numbers ICMJE | NCI-2017-01119 NCI-2017-01119 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) NRG-BR004 ( Other Identifier: NRG Oncology ) NRG-BR004 ( Other Identifier: CTEP ) U10CA180868 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | National Cancer Institute (NCI) | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | NRG Oncology | ||||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||||
Verification Date | May 2022 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |