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

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

Sponsors

Lead Sponsor: Hoffmann-La Roche

Source Hoffmann-La Roche
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.

Overall Status Active, not recruiting
Start Date 2020-02-05
Completion Date 2025-12-27
Primary Completion Date 2022-02-01
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) Pre-dose at Cycle 8 (one cycle is 21 days)
Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) Pre-dose at Cycle 8 (one cycle is 21 days)
Secondary Outcome
Measure Time Frame
Percentage of Participants with Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment Following completion of surgery (up to 33 weeks)
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 From date of surgery to iDFS (excluding SPNBC) event (up to 5 years)
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria From date of surgery to iDFS (including SPNBC) event (up to 5 years)
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria From baseline to EFS (excluding SPNBC) event (up to 5.5 years)
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria From baseline to EFS (including SPNBC) event (up to 5.5 years)
Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria From baseline to DFRI event (up to 5.5 years)
Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival From baseline to death from any cause (up to 5.5 years)
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) From baseline until study completion (up to 5.5 years)
Number of Participants with a Symptomatic Ejection Fraction Decrease (Heart Failure) of NYHA Class III or IV and a Drop in Left Ventricular Ejection Fraction (LVEF) of at Least 10-Percentage Points from Baseline and to Below 50% From baseline until study completion (up to 5.5 years)
Number of Participants Who Died from a Definite or Probable Cardiac Death From baseline until study completion (up to 5.5 years)
Number of Participants with an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II From baseline until study completion (up to 5.5 years)
Enrollment 200
Condition
Intervention

Intervention Type: Drug

Intervention Name: Pertuzumab IV

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.

Arm Group Label: Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Intervention Type: Drug

Intervention Name: Trastuzumab IV

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.

Arm Group Label: Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Intervention Type: Drug

Intervention Name: Pertuzumab and Trastuzumab FDC SC

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.

Arm Group Label: Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

Intervention Type: Drug

Intervention Name: Doxorubicin

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: Cyclophosphamide

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: Docetaxel

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: Surgery

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: Post-Operative Radiotherapy

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: Hormone Therapy

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.

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Clinical Trials Study Director Hoffmann-La Roche
Overall Contact

Last Name: Reference Study ID Number: YO41137 www.roche.com/about_roche/roche_worldwide.htm

Phone: 888-662-6728 (U.S. Only)

Email: [email protected]

Location
Facility:
Peking University People's Hospital | Beijing, 100044, China
Beijing Cancer Hospital | Beijing, 100142, China
The First Hospital of Jilin University | Changchun City, 130021, China
Jilin Cancer Hospital | Changchun, 132013, China
West China Hospital, Sichuan University | Chengdu, 610041, China
The 900th Hospital of PLA joint service support force | Fuzhou, 110016, China
Sun Yet-sen University Cancer Center | Guangzhou, 510060, China
Zhejiang Cancer Hospital; Breast Surgery | Hangzhou City, 310022, China
Harbin Medical University Cancer Hospital | Harbin, 150081, China
Shandong Cancer Hospital | Jinan, 250117, China
Jiangsu Province Hospital | Nanjing, 210036, China
The Affiliated Hospital of Medical College Qingdao University | Qingdao, 266003, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Shanghai City, 200025, China
Fudan University Shanghai Cancer Center | Shanghai City, 200120, China
Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province) | Shijiazhuang, 050035, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan City, 430023, China
Hubei Cancer Hospital | Wuhan, 430079, China
The First Affiliated Hospital of Xian Jiao Tong University | Xi'an City, 710061, China
Location Countries

China

Verification Date

2021-07-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Type: Active Comparator

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.

Label: Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

Type: Experimental

Description: 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) of 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.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News