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A Study to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel Versus Placebo + Trastuzumab + Docetaxel in Previously Untreated Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (MBC)

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ClinicalTrials.gov Identifier: NCT02896855
Recruitment Status : Active, not recruiting
First Posted : September 12, 2016
Results First Posted : July 10, 2019
Last Update Posted : December 23, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 7, 2016
First Posted Date  ICMJE September 12, 2016
Results First Submitted Date  ICMJE June 18, 2019
Results First Posted Date  ICMJE July 10, 2019
Last Update Posted Date December 23, 2019
Actual Study Start Date  ICMJE September 13, 2016
Actual Primary Completion Date June 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2019)
  • Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From date of randomization until date of first documented PD or date of death from any cause within 18 weeks after the last tumor assessment, whichever occurs first (up to approximately 3 years) ]
    Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day). At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Percentage of Participants With 1 Year of Progression-Free Survival, as Determined by the Investigator Using RECIST v1.1 [ Time Frame: From date of randomization until date of first documented PD or date of death from any cause within 18 weeks after the last tumor assessment, whichever occurs first (up to 1 year) ]
    Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants with 1 year of PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) and 59.46 (16.80) weeks, respectively.
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2016)
Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to approximately 3 years ]
Change History Complete list of historical versions of study NCT02896855 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2019)
  • Overall Survival [ Time Frame: From date of randomization until the date of death from any cause (up to approximately 3 years) ]
    Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate median OS for each treatment arm. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Percentage of Participants With 1 Year of Overall Survival [ Time Frame: From date of randomization until the date of death from any cause (up to 1 year) ]
    Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate the percentage of participants with 1 year of OS. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1 [ Time Frame: At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (up to approximately 3 years) ]
    An objective response was defined as a complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Also per RECIST v1.1, stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study; PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The same assessment technique must be used throughout the study for evaluating a particular lesion, and the same investigator should assess all tumor responses for each participant. Participants without a post-baseline tumor assessment were considered non-responders.
  • Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1 [ Time Frame: From date of first occurrence of documented objective response to date of progressive disease or date of death from any cause within 18 weeks after the last tumor assessment, whichever occurs first (up to approximately 3 years) ]
    Duration of objective response was defined as the time from the first occurrence of a documented objective response (complete response [CR] or partial response [PR]) to the time of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. The Kaplan-Meier approach was used to estimate median duration of objective response. Data for participants who did not have an event were censored at the time of the last tumor assessment (if no tumor assessments were performed after baseline visit, at randomization plus 1 day). At the primary completion date, mean (standard deviation) duration of time on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Number of Participants With at Least One Adverse Event [ Time Frame: From Baseline up to 3 years after treatment discontinuation ]
    The number of participants experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Number of Participants With at Least One Grade ≥3 Adverse Event [ Time Frame: From Baseline up to 3 years after treatment discontinuation ]
    The adverse event severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) was used for assessing the severity of adverse events. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment [ Time Frame: From Baseline up to 3 years after treatment discontinuation ]
    At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan [ Time Frame: Baseline, every 9 weeks from the date of randomization until the treatment discontinuation visit, then every 6 months for the first year and annually thereafter for up to 3 years ]
    The number of participants with symptomatic left ventricular systolic dysfunction (LVSD) at any time during the study, as determined using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan, were summarized by treatment arm. Symptomatic LVSD was evaluated according to NCI CTCAE v4.0 (for "heart failure") and the New York Heart Association (NYHA) classification. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Number of Participants With an Asymptomatic Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan [ Time Frame: Baseline, every 9 weeks from the date of randomization until the treatment discontinuation visit, then every 6 months for the first year and annually thereafter for up to 3 years ]
    An asymptomatic LVEF event is reported as an adverse event of "ejection fraction decreased" and is defined as either of the following: an absolute decrease in LVEF of ≥10 percentage points from baseline to an LVEF of <50%; or an asymptomatic decrease in LVEF requiring treatment or leading to discontinuation of pertuzumab (or placebo) and trastuzumab. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Change From Baseline in LVEF Over Time, as Determined Using ECHO or MUGA Scan [ Time Frame: Baseline, every 9 weeks from the date of randomization until the treatment discontinuation visit, then every 6 months for the first year and annually thereafter for up to 3 years ]
    Here, we report the change from baseline in LVEF over time. Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator must have decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
  • Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study [ Time Frame: Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to approximately 3 years) ]
    The baseline left ventricular ejection fraction (LVEF) and change from baseline to the maximum on-treatment decrease in LVEF at any point during the study are reported here. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible. At the primary completion date, the mean (standard deviation) duration of time that participants were on study in Arms A and B were 57.74 (19.14) weeks and 59.46 (16.80) weeks, respectively.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2016)
  • Percentage of Participants With Symptomatic Left Ventricular Systolic Dysfunction, as Determined Using Echocardiography (ECHO) or Multiple-gated Acquisition (MUGA) Scan [ Time Frame: Baseline up to approximately 3 years ]
  • Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction, as Determined Using ECHO or MUGA Scan [ Time Frame: Baseline up to approximately 3 years ]
  • LVEF as Determined Using ECHO or MUGA Scan [ Time Frame: Baseline, every 9 weeks thereafter up to approximately 3 years ]
  • Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to approximately 3 years ]
  • Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to assessed up to approximately 3 years ]
  • Duration of Objective Response as Determined by the Investigator Using RECIST v1.1 [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to assessed up to approximately 3 years ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel Versus Placebo + Trastuzumab + Docetaxel in Previously Untreated Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer (MBC)
Official Title  ICMJE A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab+Herceptin+Docetaxel Versus Placebo+Herceptin+Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
Brief Summary This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial in China will evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel compared with placebo + trastuzumab + docetaxel in participants with previously untreated HER2-positive MBC.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Docetaxel
    Docetaxel (75-mg/m^2) administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
  • Drug: Pertuzumab
    Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles) administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
    Other Name: Perjeta
  • Drug: Placebo
    Placebo matched to pertuzumab administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
  • Drug: Trastuzumab
    Trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
    Other Name: Herceptin
Study Arms  ICMJE
  • Active Comparator: Arm A: Placebo + Trastuzumab + Docetaxel
    Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram [mg/kg] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter [mg/m^2]), administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Docetaxel
    • Drug: Placebo
    • Drug: Trastuzumab
  • Experimental: Arm B: Pertuzumab + Trastuzumab + Docetaxel
    Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m^2), administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Docetaxel
    • Drug: Pertuzumab
    • Drug: Trastuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 13, 2017)
243
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2016)
240
Estimated Study Completion Date  ICMJE September 24, 2020
Actual Primary Completion Date June 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease that is suitable for chemotherapy
  • HER2-positive MBC
  • Left ventricular ejection fraction (LVEF) greater than or equal to (>=) 55 percent (%) at baseline (within 42 days of randomization)
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Women of childbearing potential and men should agree to use an effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment (trastuzumab and/or pertuzumab)

Exclusion Criteria:

  • History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC)
  • History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
  • History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (<) 12 months
  • History of persistent Grade >= 2 hematologic toxicity resulting from previous adjuvant therapy
  • Grade >= 3 peripheral neuropathy at randomization
  • History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin carcinoma that has been previously treated with curative intent
  • Current clinical or radiographic evidence of central nervous system (CNS) metastases
  • History of exposure to cumulative doses of anthracyclines
  • Current uncontrolled hypertension or unstable angina
  • History of congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, or serious cardiac arrhythmia requiring treatment
  • History of myocardial infarction within 6 months of randomization
  • History of LVEF decrease to < 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
  • Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
  • Inadequate organ function within 28 days prior to randomization
  • Current severe, uncontrolled systemic disease
  • Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
  • Pregnant or lactating women
  • History of receiving any investigational treatment within 28 days of randomization
  • Current known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or active hepatitis B virus (HBV)
  • Receipt of intravenous (IV) antibiotics for infection within 14 days of randomization
  • Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
  • Known hypersensitivity to any of the protocol-specified study treatments
  • Concurrent participation in an interventional or noninterventional study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
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 China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02896855
Other Study ID Numbers  ICMJE YO29296
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP