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

NCT02586025 | Completed Phase 3 Results FDA Drug

• 1 other identifier: YO28762
• Study Type: interventional
• Target: 329
• Locations: 4 countries
• Sites: 23

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC)

  This tpCR was assessed by the IRC. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer \[AJCC\] staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point.

  At surgery (Cycle 4 Days 22-35)

Secondary Outcomes (15)

• Percentage of Participants With tpCR as Assessed by the Local Pathologist

  At surgery (Cycle 4 Days 22-35)

• Percentage of Participants With Breast Pathologic Complete Response (bpCR), Defined as ypT0/is According to the AJCC Staging System as Assessed by the IRC

  At surgery (Cycle 4 Days 22-35)

• Percentage of Participants With bpCR as Assessed by the Local Pathologist

  At surgery (Cycle 4 Days 22-35)

• 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

  At surgery (Cycle 4 Days 22-35)

• Percentage of Participants With an Objective Response (CR or PR) During Cycles 1-4, According to RECIST Version 1.1

  At surgery (Cycle 4 Days 22-35)

Study Arms (2)

Trastuzumab, Pertuzumab, and Chemotherapy

EXPERIMENTAL

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.

Drug: FEC Chemotherapy; Procedure: Surgery; Drug: Docetaxel; Drug: Pertuzumab; Drug: Trastuzumab

Trastuzumab, Placebo, and Chemotherapy

EXPERIMENTAL

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.

Drug: FEC Chemotherapy; Procedure: Surgery; Drug: Docetaxel; Drug: Placebo; Drug: Trastuzumab

Interventions

FEC Chemotherapy 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.

Trastuzumab, Pertuzumab, and Chemotherapy; Trastuzumab, Placebo, and Chemotherapy

Surgery PROCEDURE

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

Trastuzumab, Pertuzumab, and Chemotherapy; Trastuzumab, Placebo, and Chemotherapy

Docetaxel DRUG

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

Trastuzumab, Pertuzumab, and Chemotherapy; Trastuzumab, Placebo, and Chemotherapy

Pertuzumab 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)

Also known as: RO4368451

Trastuzumab, Pertuzumab, and Chemotherapy

Placebo DRUG

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

Trastuzumab, Placebo, and Chemotherapy

Trastuzumab 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.

Also known as: RO0452317

Trastuzumab, Pertuzumab, and Chemotherapy; Trastuzumab, Placebo, and Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (23)

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

Beijing, 100071, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

Fujian Medical University Union Hospital

Fuzhou, 350001, China

Location

Guangdong General Hospital

Guangzhou, 510080, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510663, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Shandong Cancer Hospital

Jinan, 250117, China

Location

Jiangsu Province Hospital

Nanjing, 210008, China

Location

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

Shanghai, 200025, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Zhejiang Cancer Hospital

Zhejiang, 310022, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Kyungpook National University Medical Center

Daegu, 41404, South Korea

Location

Ajou University Medical Center

Gyeonggi-do, 16499, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Taipei Medical University ?Shuang Ho Hospital

New Taipei City, 23561, Taiwan

Location

China Medical University Hospital; Surgery

Taichung, 404, Taiwan

Location

Mackay Memorial Hospital; Dept of Surgery

Taipei, 104, Taiwan

Location

Taipei Medical University Hospital

Taipei, 110, Taiwan

Location

Bhumibol Adulyadej Hospital; Medicine

Bangkok, 10220, Thailand

Location

Srinagarind Hospital, Khon Kaen University; Surgery

Khon Kaen, 40002, Thailand

Location

Songklanagarind Hospital; Department of Surgery

Songkhla, 90110, Thailand

Location

Related Publications (1)

• 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.

  PMID: 31647503 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Surgical Procedures, Operative; Docetaxel; pertuzumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: October 26, 2015
• Study Start: March 14, 2016
• Primary Completion: October 23, 2017
• Study Completion: March 14, 2022
• Last Updated: May 22, 2023
• Results First Posted: January 3, 2019

Record last verified: 2023-04

Locations

CN (13); KR (3); TW (4); TH (3)