Clinical trial NCT02586025: Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel
Official title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate Pertuzumab in Combination With Docetaxel and Trastuzumab as Neoadjuvant Therapy, and Pertuzumab in Combination With Trastuzumab as Adjuvant Therapy After Surgery and Chemotherapy in Patients With Early-Stage or Locally Advanced HER2-Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-10-26
Enrollment: 329
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 is an Asia-Pacific regional, randomized, double-blind, multicenter trial designed to evaluate treatment with trastuzumab + pertuzumab + docetaxel compared with trastuzumab + placebo + docetaxel in chemotherapy-naïve participants with early-stage or locally advanced HER2-positive breast cancer. The anticipated treatment duration is approximately 17 months.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed invasive breast carcinoma with a primary tumor size of more than (\>) 2 centimeters (cm) by standard local assessment technique
* Breast cancer stage at presentation: early-stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4, any N, M0)
* HER2-positive breast cancer confirmed by a Sponsor-designated central laboratory and defined as 3+ score by immunohistochemistry in \> 10 percent (%) of immunoreactive cells or HER2 gene amplification (ratio of HER2 gene signals to centromere 17 signals equal to or more than \[\>=\] 2.0) by in situ hybridization
* Known hormone receptor status (estrogen receptor and/or progesterone receptor)
* Eastern Cooperative Oncology Group Performance Status equal to or less than (\<=) 1
* Baseline left ventricular ejection fracture \>= 55% measured by echocardiography (preferred) or multiple gated acquisition scan
* Negative serum pregnancy test

Exclusion Criteria:

* Stage IV metastatic breast cancer
* Inflammatory breast cancer
* Previous anti-cancer therapy or radiotherapy for any malignancy
* History of other malignancy within 5 years prior to screening, except for appropriately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
* Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy
* Major surgical procedure unrelated to breast cancer within 4 weeks prior to randomization or from which the participant has not fully recovered
* Serious cardiac illness or medical condition
* Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
* Any abnormalities in liver, kidney or hematologic function laboratory tests immediately prior to randomization
* Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
* Pregnant or lactating

Primary outcomes:
measure: Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC)
timeFrame: At surgery (Cycle 4 Days 22-35)
Secondary outcomes:
measure: Percentage of Participants With tpCR as Assessed by the Local Pathologist
timeFrame: At surgery (Cycle 4 Days 22-35)
measure: Percentage of Participants With Breast Pathologic Complete Response (bpCR), Defined as ypT0/is According to the AJCC Staging System as Assessed by the IRC
timeFrame: At surgery (Cycle 4 Days 22-35)
measure: Percentage of Participants With bpCR as Assessed by the Local Pathologist
timeFrame: At surgery (Cycle 4 Days 22-35)
measure: Percentage of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: At surgery (Cycle 4 Days 22-35)
measure: Percentage of Participants With an Objective Response (CR or PR) During Cycles 1-4, According to RECIST Version 1.1
timeFrame: At surgery (Cycle 4 Days 22-35)
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1, 3, and 5 Years
timeFrame: From Baseline to EFS event or date last known to be alive and event-free at 1, 3, and 5 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Disease-Free Survival (DFS) at 1, 3, and 5 Years
timeFrame: From surgery (Cycle 4: Days 22-35) to DFS event or date last known to be alive and event-free at 1, 3, and 5 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1, 3, and 5 Years
timeFrame: From Baseline to OS event or date last known to be alive at 1, 3, and 5 years
measure: Percentage of Participants With at Least One Adverse Event (AE) During the Neoadjuvant Treatment Period
timeFrame: Baseline up to end of Cycle 4 (1 cycle = 21 days)
measure: Percentage of Participants With at Least One AE During the Adjuvant Treatment Period
timeFrame: From Cycle 5 (1 cycle = 21 days) up to 42 days after the last dose in Cycle 20 Day 1 (approximately 1 year)
measure: Percentage of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period
timeFrame: From end of overall study treatment until disease progression or until 5 years after randomization of the last patient, whichever occurred first (up to 6 years)
measure: Percentage of Participants Who Experienced a Primary Cardiac Event
timeFrame: From Baseline until end of study (up to 6 years)
measure: Percentage of Participants Who Experienced a Secondary Cardiac Event
timeFrame: From Baseline until end of study (up to 6 years)
measure: Maximum Change From Baseline in LVEF
timeFrame: Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)
measure: Change From Baseline in LVEF Over Time
timeFrame: Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Fuzhou City
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou City
country: China
facility: Sun Yet-sen University Cancer Center
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University ?Shuang Ho Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital; Surgery
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital; Dept of Surgery
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Bangkok
country: Thailand
facility: Bhumibol Adulyadej Hospital; Medicine
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital, Khon Kaen University; Surgery
city: Songkla
country: Thailand
facility: Songklanagarind Hospital; Department of Surgery
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. doi: 10.1001/jamaoncol.2019.3692. Epub 2020 Mar 12.