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

NCT ID: NCT02586025

Last Updated: 2023-05-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

329 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-14

Study Completion Date

2022-03-14

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Trastuzumab, Pertuzumab, and Chemotherapy

Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC): trastuzumab and pertuzumab up to 1 year total.

Group Type EXPERIMENTAL

FEC Chemotherapy

Intervention Type DRUG

Fluorouracil 500-600 milligrams per square meter (mg/m2), epirubicin 90-120 mg/m2, and cyclophosphamide 500-600 mg/m2 by intravenous (IV) infusion every 3 weeks for three cycles (Cycles 5-7). FEC chemotherapeutic agents will be administered following surgery on Day 1 of each specified cycle.

Surgery

Intervention Type PROCEDURE

All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Docetaxel

Intervention Type DRUG

Docetaxel IV infusion in 3-week cycles. Neoadjuvant treatment: 75 mg/m2 for Cycles 1-4.

Pertuzumab

Intervention Type DRUG

Pertuzumab IV infusion in 3-week cycles. Prior to surgery (neoadjuvant treatment): 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4. After surgery and 3 cycles of FEC chemotherapy (adjuvant treatment): 840 mg loading dose for Cycle 8, followed by 420 mg for Cycles 9-20)

Trastuzumab

Intervention Type DRUG

Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4. Adjuvant treatment: 8 mg/kg loading dose for Cycle 8, followed by 6 mg/kg for Cycles 9-20.

Trastuzumab, Placebo, and Chemotherapy

Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy: trastuzumab and placebo up to 1 year total.

Group Type EXPERIMENTAL

FEC Chemotherapy

Intervention Type DRUG

Fluorouracil 500-600 milligrams per square meter (mg/m2), epirubicin 90-120 mg/m2, and cyclophosphamide 500-600 mg/m2 by intravenous (IV) infusion every 3 weeks for three cycles (Cycles 5-7). FEC chemotherapeutic agents will be administered following surgery on Day 1 of each specified cycle.

Surgery

Intervention Type PROCEDURE

All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Docetaxel

Intervention Type DRUG

Docetaxel IV infusion in 3-week cycles. Neoadjuvant treatment: 75 mg/m2 for Cycles 1-4.

Placebo

Intervention Type DRUG

Placebo by IV infusion in 3-week cycles as neoadjuvant treatment (Cycles 1-4)and as adjuvant treatment (Cycles 8-20)

Trastuzumab

Intervention Type DRUG

Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4. Adjuvant treatment: 8 mg/kg loading dose for Cycle 8, followed by 6 mg/kg for Cycles 9-20.

Interventions

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FEC Chemotherapy

Fluorouracil 500-600 milligrams per square meter (mg/m2), epirubicin 90-120 mg/m2, and cyclophosphamide 500-600 mg/m2 by intravenous (IV) infusion every 3 weeks for three cycles (Cycles 5-7). FEC chemotherapeutic agents will be administered following surgery on Day 1 of each specified cycle.

Intervention Type DRUG

Surgery

All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

Intervention Type PROCEDURE

Docetaxel

Docetaxel IV infusion in 3-week cycles. Neoadjuvant treatment: 75 mg/m2 for Cycles 1-4.

Intervention Type DRUG

Pertuzumab

Pertuzumab IV infusion in 3-week cycles. Prior to surgery (neoadjuvant treatment): 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4. After surgery and 3 cycles of FEC chemotherapy (adjuvant treatment): 840 mg loading dose for Cycle 8, followed by 420 mg for Cycles 9-20)

Intervention Type DRUG

Placebo

Placebo by IV infusion in 3-week cycles as neoadjuvant treatment (Cycles 1-4)and as adjuvant treatment (Cycles 8-20)

Intervention Type DRUG

Trastuzumab

Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4. Adjuvant treatment: 8 mg/kg loading dose for Cycle 8, followed by 6 mg/kg for Cycles 9-20.

Intervention Type DRUG

Other Intervention Names

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RO4368451 RO0452317

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)

Beijing, , China

Site Status

the First Hospital of Jilin University

Changchun, , China

Site Status

Jilin Cancer Hospital

Changchun, , China

Site Status

Fujian Medical University Union Hospital

Fuzhou, , China

Site Status

Guangdong General Hospital

Guangzhou, , China

Site Status

Sun Yet-sen University Cancer Center

Guangzhou, , China

Site Status

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status

Shandong Cancer Hospital

Jinan, , China

Site Status

Jiangsu Province Hospital

Nanjing, , China

Site Status

Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)

Shanghai, , China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Zhejiang Cancer Hospital

Zhejiang, , China

Site Status

Henan Cancer Hospital

Zhengzhou, , China

Site Status

Kyungpook National University Medical Center

Daegu, , South Korea

Site Status

Ajou University Medical Center

Gyeonggi-do, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

Taipei Medical University ?Shuang Ho Hospital

New Taipei City, , Taiwan

Site Status

China Medical University Hospital; Surgery

Taichung, , Taiwan

Site Status

Mackay Memorial Hospital; Dept of Surgery

Taipei, , Taiwan

Site Status

Taipei Medical University Hospital

Taipei, , Taiwan

Site Status

Bhumibol Adulyadej Hospital; Medicine

Bangkok, , Thailand

Site Status

Srinagarind Hospital, Khon Kaen University; Surgery

Khon Kaen, , Thailand

Site Status

Songklanagarind Hospital; Department of Surgery

Songkhla, , Thailand

Site Status

Countries

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China South Korea Taiwan Thailand

References

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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.

Reference Type DERIVED
PMID: 31647503 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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YO28762

Identifier Type: -

Identifier Source: org_study_id

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