A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer
Condition: HER2-Positive Early Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC); Pertuzumab IV; Trastuzumab IV
Intervention description: PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg pertuzumab and 600 mg trastuzumab is then followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks (Q3W).; Pertuzumab will be administered intravenously (IV) as a fixed non-weight-based dose of 840-mg IV loading dose and then 420-mg IV maintenance dose Q3W.; Trastuzumab will be administered intravenously (IV) as an 8-mg/kg IV loading dose and then 6 mg/kg IV maintenance dose Q3W.
Intervention MeSH terms: Trastuzumab; Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase II, randomized, multicentre, multinational, open-label, cross-over study in
      adult patients who have completed neoadjuvant chemotherapy with neoadjuvant pertuzumab and
      trastuzumab and have undergone surgical treatment of human epidermal growth factor receptor 2
      (HER2)-positive early breast cancer. The study will consist of two adjuvant treatment
      periods: a treatment cross-over period and a treatment continuation period. It will evaluate
      participant-reported preference for a subcutaneously administered fixed-dose combination
      formulation (FDC SC) of pertuzumab and trastuzumab compared with intravenously (IV)
      administered pertuzumab and trastuzumab formulations. The study will also evaluate
      participant-reported satisfaction with pertuzumab and trastuzumab FDC SC and health-related
      quality of life outcomes; healthcare professionals' perceptions of time/resource use and
      convenience of pertuzumab and trastuzumab FDC SC compared with pertuzumab and trastuzumab IV
      formulations; as well as the safety and efficacy of each study regimen.
    

Eligibility criteria:

        Inclusion Criteria:

        Disease-specific criteria:

          -  Female or male with histologically confirmed, HER2-positive (HER2+) inflammatory,
             locally advanced or early-stage breast cancer who have received neoadjuvant pertuzumab
             and trastuzumab and have completed neoadjuvant chemotherapy and subsequently undergone
             surgery for their breast cancer.

          -  HER2+ breast cancer assessed at the local laboratory prior to initiation of
             neoadjuvant therapy. HER2+ status must be determined based on breast biopsy material
             obtained prior to neoadjuvant treatment and is 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 chromosome 17 copies.

          -  Hormone receptor status of the primary tumour determined by local assessment. Hormone
             receptor status may be either positive or negative.

          -  Completed all neoadjuvant chemotherapy and surgery. Adjuvant radiotherapy may be
             planned or ongoing at study entry and adjuvant hormone therapy is allowed during the
             study. Note that study treatment cannot be initiated within <2 weeks of surgery but
             must be initiated ≤9 weeks from the last administration of systemic neoadjuvant
             therapy.

          -  No evidence of residual, locally recurrent or metastatic disease after completion of
             surgery. Patients with clinical suspicion of metastases must undergo radiological
             assessments per institutional practice to rule out distant disease.

          -  Wound healing after breast cancer surgery adequate per investigator's assessment to
             allow initiation of study treatment within ≤9 weeks of last systemic neoadjuvant
             therapy

          -  No adjuvant chemotherapy planned. Note that adjuvant hormonal treatment is allowed
             during the study.

        General criteria:

          -  Ability to comply with the study protocol, in the investigator's judgment

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Intact skin at planned site of subcutaneous injections (thigh)

          -  Left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or
             multiple-gated acquisition (MUGA) scan within 28 days of study randomization

          -  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

          -  For women of childbearing potential: agreement to remain abstinent or use
             contraceptive measures, and agreement to refrain from donating eggs, Women must remain
             abstinent or use non-hormonal contraceptive methods with a failure rate of <1% per
             year, or two effective non-hormonal contraceptive methods during the study treatment
             periods and for 7 months after the last dose of study treatment

          -  For men: agreement to remain abstinent or use a condom, and agreement to refrain from
             donating sperm, men must remain abstinent or use a condom during the study treatment
             periods and for seven months after the last dose of study treatment to avoid exposing
             the embryo. Men must refrain from donating sperm during this same period

          -  A negative serum pregnancy test must be available prior to randomization for women of
             childbearing potential

        Exclusion Criteria:

        Cancer-specific criteria:

          -  Stage IV (metastatic) breast cancer

          -  Current or prior history of active malignancy within the last five years.
             Appropriately treated non-melanoma skin cancer; in situ carcinomas, including cervix,
             colon, or skin; or Stage I uterine cancer within the last five years are allowed

          -  Previous systemic therapy for treatment or prevention of breast cancer, except
             neoadjuvant Perjeta, Herceptin and chemotherapy for current breast cancer

        General criteria:

          -  Investigational treatment within four weeks of enrolment

          -  Serious cardiac illness or medical conditions

          -  History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such
             as structural heart disease, coronary heart disease, clinically significant
             electrolyte abnormalities, or family history of sudden unexplained death or long QT
             syndrome

          -  Inadequate bone marrow, renal and impaired liver function

          -  Current severe, uncontrolled systemic disease that may interfere with planned
             treatment

          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within
             seven months after the last dose of study treatment. Women of childbearing potential
             must have a negative serum pregnancy test result within seven days prior to initiation
             of study treatment

          -  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, autoimmune
             hepatic disorders, or sclerosing cholangitis

          -  Concurrent, serious, uncontrolled infections, or known infection with human
             immunodeficiency virus (HIV)

          -  Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins

          -  Current chronic daily treatment with corticosteroids