Clinical trial NCT02896855: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-09-12
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease that is suitable for chemotherapy
* HER2-positive metastatic breast cancer (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

Primary outcomes:
measure: Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1
timeFrame: At 1, 2, and 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years
timeFrame: At 1, 2, and 3 Years
measure: 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
timeFrame: At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
measure: Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1
timeFrame: From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
measure: Number of Participants With at Least One Adverse Event
timeFrame: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
measure: Number of Participants With at Least One Grade ≥3 Adverse Event
timeFrame: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
measure: Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment
timeFrame: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
measure: Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
timeFrame: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
measure: Number of Participants With an Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan
timeFrame: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
measure: Number of Participants by the LVEF Abnormality Status Categories Over Time, as Determined by the Change From Baseline in LVEF Using ECHO or MUGA Scans
timeFrame: Baseline, Weeks 9, 18, 27, 36, 45, 54, 63, 72, 81, 90, 99, 108, 117, 126, 135, 144, 153, 162, 171, 180, 189, 198, 207, 216, and 225, Study Drug Discontinuation Visit (up to 4 years, 4 months), and Treatment-Free Follow-Up at 6 months, and 1 and 2 years
measure: Baseline LVEF and Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study
timeFrame: Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to 4 years, 4 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: CHINESE ACADEMY OF MEDICAL SCIENCE; CANCER INST. & HOSPITAL; Medical ward
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Changzhou
country: China
facility: Changzhou First People's Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Fuzhou
country: China
facility: The 900th Hospital of PLA joint service support force
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanjing City
country: China
facility: Jiangsu Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu province hospital; surgery on galactophore
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shenyang
country: China
facility: First Hospital of China Medical University
city: Shenyang
country: China
facility: Liaoning cancer Hospital & Institute
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Xu B, Li W, Zhang Q, Shao Z, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhang H, Lei G, Restuccia E. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2020 Aug;182(3):689-697. doi: 10.1007/s10549-020-05728-w. Epub 2020 Jun 20.