Clinical Trials /

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

NCT04024462

Description:

This study will evaluate the pharmacokinetics, efficacy, and safety of the fixed-dose combination (FDC) of pertuzumab and trastuzumab for subcutaneous (SC) administration 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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: YO41137
  • NCT ID: NCT04024462

Conditions

  • HER2-positive Early Breast Cancer

Interventions

DrugSynonymsArms
Pertuzumab IVPerjeta, RO4368451Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
Trastuzumab IVHerceptin, RO0452317Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
FDC of Pertuzumab and Trastuzumab SCRG6264, RO7198574Arm B: FDC of Pertuzumab and Trastuzumab SC + Chemotherapy
DoxorubicinArm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
CyclophosphamideArm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
DocetaxelArm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy
Hormone TherapyArm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

Purpose

This study will evaluate the pharmacokinetics, efficacy, and safety of the fixed-dose combination (FDC) of pertuzumab and trastuzumab for subcutaneous (SC) administration 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.

Trial Arms

NameTypeDescriptionInterventions
Arm A: Pertuzumab IV + Trastuzumab IV + ChemotherapyActive ComparatorParticipants 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.
  • Pertuzumab IV
  • Trastuzumab IV
  • Doxorubicin
  • Cyclophosphamide
  • Docetaxel
  • Hormone Therapy
Arm B: FDC of Pertuzumab and Trastuzumab SC + ChemotherapyExperimentalParticipants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The fixed-dose combination (FDC) of pertuzumab and trastuzumab 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 FDC of pertuzumab and trastuzumab SC for a total of 18 cycles.
  • FDC of Pertuzumab and Trastuzumab SC
  • Doxorubicin
  • Cyclophosphamide
  • Docetaxel
  • Hormone 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)
Time Frame:Pre-dose at Cycle 8 (one cycle is 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment
Time Frame:Following completion of surgery (up to 33 weeks)
Safety Issue:
Description:tpCR is defined as eradication of invasive disease in the breast and axilla (i.e., ypT0/isypN0)
Measure: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
Time Frame:From date of surgery to iDFS (excluding SPNBC) event (up to 5 years)
Safety Issue:
Description: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.
Measure:Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria
Time Frame:From date of surgery to iDFS (including SPNBC) event (up to 5 years)
Safety Issue:
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).
Measure:Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria
Time Frame:From baseline to EFS (excluding SPNBC) event (up to 5.5 years)
Safety Issue:
Description: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.
Measure:Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria
Time Frame:From baseline to EFS (including SPNBC) event (up to 5.5 years)
Safety Issue:
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).
Measure:Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria
Time Frame:From baseline to DFRI event (up to 5.5 years)
Safety Issue:
Description:DRFI is defined as the time between randomization and the date of distant breast cancer recurrence.
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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%
Time Frame:From baseline until study completion (up to 5.5 years)
Safety Issue:
Description:New York Heart Association (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.
Measure:Number of Participants Who Died from a Definite or Probable Cardiac Death
Time Frame:From baseline until study completion (up to 5.5 years)
Safety Issue:
Description: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, infarction, arrhythmia) without documented etiology.
Measure:Number of Participants with an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II
Time Frame:From baseline until study completion (up to 5.5 years)
Safety Issue:
Description:An LVSD ("Ejection fraction decreased") of NYHA Class II is defined as an LVEF decrease of ≥10-percentage points below the baseline measurement to an absolute LVEF value of <50%, confirmed by a second assessment within approximately 3 weeks confirming a decrease of ≥10-percentage points below the baseline measurement and to an absolute LVEF value of <50%.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated