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A Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese Participants With HER2-Positive Early Breast Cancer

Primary Purpose

HER2-positive Early Breast Cancer

Status

Active

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Pertuzumab IV

Trastuzumab IV

Pertuzumab and Trastuzumab FDC SC

Doxorubicin

Cyclophosphamide

Docetaxel

Surgery

Post-Operative Radiotherapy

Hormone Therapy

About this trial

This is an interventional treatment trial for HER2-positive Early Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ability to comply with the study protocol, in the investigator's judgment
Eastern Cooperative Oncology Group (ECOG) Performance Status greater or equal to (≤)1
Stage II-IIIC (T2-T4 plus any N, or any T plus N1-3, M0), locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer
Primary tumor greater than (>)2 centimeters (cm) in diameter, or node-positive disease (clinically or on imaging, and node positivity confirmed with cytology and/or histopathology)
Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies
Hormone receptor status of the primary tumor, centrally confirmed
Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy
Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue for central confirmation of HER2, hormone receptor status, and PIK3CA mutational analyses
Baseline left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective non-hormonal contraceptive method with a failure rate of less than (<)1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as specified in the protocol
A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women <12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)
No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment

Exclusion Criteria:

Stage IV (metastatic) breast cancer
History of invasive breast cancer
History of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin
Have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, endocrine therapy [selective estrogen receptor modulators, aromatase inhibitors], and antitumor vaccines) for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer
Have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast
High-risk for breast cancer and have received chemopreventative drugs in the past
Multicentric (multiple tumors involving more than one quadrant) breast cancer, unless all tumors are HER2-positive
Bilateral breast cancer
Have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes
Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy
Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy
Treatment with any investigational drug within 28 days prior to randomization
Serious cardiac illness or medical conditions
Inadequate bone marrow function
Impaired liver function
Inadequate renal function with serum creatinine >1.5X upper limit of normal (ULN)
Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders)
Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis
Concurrent, serious, uncontrolled infections, or known infection with HIV
Known hypersensitivity to study drugs, excipients, and/or murine proteins
Current chronic daily treatment with corticosteroids (dose >10 milligrams [mg] methylprednisolone or equivalent excluding inhaled steroids)
History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, colon, skin, and/or non-melanoma skin carcinoma
History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome

Sites / Locations

Peking University People's Hospital
Beijing Cancer Hospital
The First Hospital of Jilin University
Jilin Cancer Hospital
West China Hospital, Sichuan University
The 900th Hospital of PLA joint service support force
Sun Yet-sen University Cancer Center
Zhejiang Cancer Hospital; Breast Surgery
Harbin Medical University Cancer Hospital
Shandong Cancer Hospital
Jiangsu Province Hospital
The Affiliated Hospital of Medical College Qingdao University
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Fudan University Shanghai Cancer Center
Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Hubei Cancer Hospital
The First Affiliated Hospital of Xian Jiao Tong University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

Arm Description

Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab will be given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles.

Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of the PH FDC SC for a total of 18 cycles.

Outcomes

Primary Outcome Measures

Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)

The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement.

Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)

The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement.

Secondary Outcome Measures

Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment

Total pathological complete response (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated.

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria

iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria

iDFS including SPNBC is defined in the same way as iDFS but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria

EFS (excluding SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse.

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria

EFS including SPNBC is defined in the same way as EFS, but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria

DRFI is defined as the time between randomization and the date of distant breast cancer recurrence.

Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival

Number of Participants With at Least One Adverse Event by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4)

Number of Participants With a Primary Cardiac Event

A primary cardiac event is defined as either a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III/IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%, or a definite or probable cardiac death. NYHA Class III is defined as: marked limitation of physical activity; comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. NYHA Class IV is defined as: Inability to carry on any physical activity without discomfort; symptoms of cardiac insufficiency at rest; if any physical activity is undertaken, discomfort is increased. Definite cardiac death is defined as death due to heart failure, myocardial infarction, or documented primary arrhythmia. Probable cardiac death is defined as sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, etc.) without documented etiology.

Number of Participants With a Secondary Cardiac Event, Defined as an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II

An LVSD ("Ejection fraction decreased") of NYHA Class II is defined as a left ventricular ejection fraction (LVEF) decrease of ≥10-percentage points below the baseline measurement to an absolute LVEF value of <50%, confirmed by a second LVEF assessment within approximately 3 weeks also showing a documented drop.

Full Information

NCT ID

NCT04024462

First Posted

July 17, 2019

Last Updated

October 3, 2023

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT04024462

Brief Title

A Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese Participants With HER2-Positive Early Breast Cancer

Official Title

A Phase III, Randomized, Multicenter, Open-Label, Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese Patients With HER2-Positive Early Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 5, 2020 (Actual)

Primary Completion Date

December 13, 2021 (Actual)

Study Completion Date

November 11, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study will evaluate the pharmacokinetics, efficacy, and safety of the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) as compared with those of the pertuzumab intravenous (IV) and trastuzumab IV formulations in Chinese participants with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HER2-positive Early Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

200 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Arm Type

Active Comparator

Arm Description

Arm Title

Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pertuzumab IV

Other Intervention Name(s)

Perjeta, RO4368451

Intervention Description

Pertuzumab will be administered as a fixed non-weight-based loading dose of 840-milligrams (mg) IV and then a 420-mg IV maintenance dose Q3W.

Intervention Type

Drug

Intervention Name(s)

Trastuzumab IV

Other Intervention Name(s)

Herceptin, RO0452317

Intervention Description

Trastuzumab will be administered as an 8-milligram per kilogram of body weight (mg/kg) IV loading dose and then 6 mg/kg IV maintenance dose Q3W.

Intervention Type

Drug

Intervention Name(s)

Pertuzumab and Trastuzumab FDC SC

Other Intervention Name(s)

Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, PHESGO™, PH FDC SC, RG6264, RO7198574

Intervention Description

The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be administered SC at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab Q3W.

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Description

Doxorubicin 60 milligrams per meter squared of body surface area (mg/m^2) will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Cyclophosphamide 600 mg/m^2 will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

Docetaxel 75 mg/m^2 will be administered IV on Day 1 of Cycle 5. At the investigator's discretion the dose may be escalated to 100 mg/m^2 IV for Cycles 6-8 (Q3W) provided no dose-limiting toxicity occurs.

Intervention Type

Procedure

Intervention Name(s)

Surgery

Intervention Description

Participants in both cohorts are scheduled to undergo surgery after 8 cycles of neoadjuvant therapy. Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice.

Intervention Type

Radiation

Intervention Name(s)

Post-Operative Radiotherapy

Intervention Description

If indicated, radiotherapy is given after chemotherapy and surgery, during adjuvant HER2-targeted therapy and hormone therapy (for hormone-receptor positive disease).

Intervention Type

Drug

Intervention Name(s)

Hormone Therapy

Intervention Description

For hormone receptor positive breast cancer, tamoxifen or aromatase inhibitors will be allowed as adjuvant hormone therapy for postmenopausal participants and with ovarian suppression or ablation for premenopausal participants in countries where it has been registered for this indication. Its use must be consistent with the registered label. Hormone therapy is given after chemotherapy and surgery during adjuvant HER2-targeted therapy.

Primary Outcome Measure Information:

Title

Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)

Description

Time Frame

Pre-dose at Cycle 8 (one cycle is 21 days)

Title

Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)

Description

Time Frame

Pre-dose at Cycle 8 (one cycle is 21 days)

Secondary Outcome Measure Information:

Title

Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment

Description

Time Frame

Following completion of surgery (up to 33 weeks)

Title

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria

Description

Time Frame

From date of surgery to iDFS (excluding SPNBC) event (up to 5 years)

Title

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria

Description

iDFS including SPNBC is defined in the same way as iDFS but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

Time Frame

From date of surgery to iDFS (including SPNBC) event (up to 5 years)

Title

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria

Description

Time Frame

From baseline to EFS (excluding SPNBC) event (up to 5.5 years)

Title

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria

Description

EFS including SPNBC is defined in the same way as EFS, but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).

Time Frame

From baseline to EFS (including SPNBC) event (up to 5.5 years)

Title

Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria

Description

DRFI is defined as the time between randomization and the date of distant breast cancer recurrence.

Time Frame

From baseline to DFRI event (up to 5.5 years)

Title

Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival

Time Frame

From baseline to death from any cause (up to 5.5 years)

Title

Number of Participants With at Least One Adverse Event by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4)

Time Frame

From baseline until study completion (up to 5.5 years)

Title

Number of Participants With a Primary Cardiac Event

Description

Time Frame

From baseline until study completion (up to 5.5 years)

Title

Number of Participants With a Secondary Cardiac Event, Defined as an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II

Description

Time Frame

From baseline until study completion (up to 5.5 years)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability to comply with the study protocol, in the investigator's judgment Eastern Cooperative Oncology Group (ECOG) Performance Status greater or equal to (≤)1 Stage II-IIIC (T2-T4 plus any N, or any T plus N1-3, M0), locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer Primary tumor greater than (>)2 centimeters (cm) in diameter, or node-positive disease (clinically or on imaging, and node positivity confirmed with cytology and/or histopathology) Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies Hormone receptor status of the primary tumor, centrally confirmed Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue for central confirmation of HER2, hormone receptor status, and PIK3CA mutational analyses Baseline left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective non-hormonal contraceptive method with a failure rate of less than (<)1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as specified in the protocol A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women <12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus) No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment Exclusion Criteria: Stage IV (metastatic) breast cancer History of invasive breast cancer History of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin Have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, endocrine therapy [selective estrogen receptor modulators, aromatase inhibitors], and antitumor vaccines) for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer Have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast High-risk for breast cancer and have received chemopreventative drugs in the past Multicentric (multiple tumors involving more than one quadrant) breast cancer, unless all tumors are HER2-positive Bilateral breast cancer Have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy Treatment with any investigational drug within 28 days prior to randomization Serious cardiac illness or medical conditions Inadequate bone marrow function Impaired liver function Inadequate renal function with serum creatinine >1.5X upper limit of normal (ULN) Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders) Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis Concurrent, serious, uncontrolled infections, or known infection with HIV Known hypersensitivity to study drugs, excipients, and/or murine proteins Current chronic daily treatment with corticosteroids (dose >10 milligrams [mg] methylprednisolone or equivalent excluding inhaled steroids) History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, colon, skin, and/or non-melanoma skin carcinoma History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Peking University People's Hospital

City

Beijing

ZIP/Postal Code

100044

Country

China

Facility Name

Beijing Cancer Hospital

City

Beijing

ZIP/Postal Code

100142

Country

China

Facility Name

The First Hospital of Jilin University

City

Changchun City

ZIP/Postal Code

130021

Country

China

Facility Name

Jilin Cancer Hospital

City

Changchun

ZIP/Postal Code

132013

Country

China

Facility Name

West China Hospital, Sichuan University

City

Chengdu

ZIP/Postal Code

610041

Country

China

Facility Name

The 900th Hospital of PLA joint service support force

City

Fuzhou

ZIP/Postal Code

110016

Country

China

Facility Name

Sun Yet-sen University Cancer Center

City

Guangzhou City

ZIP/Postal Code

510663

Country

China

Facility Name

Zhejiang Cancer Hospital; Breast Surgery

City

Hangzhou City

ZIP/Postal Code

310022

Country

China

Facility Name

Harbin Medical University Cancer Hospital

City

Harbin

ZIP/Postal Code

150081

Country

China

Facility Name

Shandong Cancer Hospital

City

Jinan

ZIP/Postal Code

250117

Country

China

Facility Name

Jiangsu Province Hospital

City

Nanjing

ZIP/Postal Code

210008

Country

China

Facility Name

The Affiliated Hospital of Medical College Qingdao University

City

Qingdao

ZIP/Postal Code

266003

Country

China

Facility Name

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

City

Shanghai City

ZIP/Postal Code

200025

Country

China

Facility Name

Fudan University Shanghai Cancer Center

City

Shanghai City

ZIP/Postal Code

200120

Country

China

Facility Name

Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)

City

Shijiazhuang

ZIP/Postal Code

050035

Country

China

Facility Name

Union Hospital Tongji Medical College Huazhong University of Science and Technology

City

Wuhan City

ZIP/Postal Code

430023

Country

China

Facility Name

Hubei Cancer Hospital

City

Wuhan

ZIP/Postal Code

430079

Country

China

Facility Name

The First Affiliated Hospital of Xian Jiao Tong University

City

Xi'an City

ZIP/Postal Code

710061

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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