Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Intervenciones

drug

Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC)

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).

drug

Pertuzumab IV

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.

drug

Trastuzumab IV

Trastuzumab will be administered intravenously (IV) as an 8-mg/kg IV loading dose and then 6 mg/kg IV maintenance dose Q3W.

A Randomized, Multicenter, Open-Label Cross-Over Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Patients With HER2-Positive Early Breast Cancer

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC)

Pertuzumab IV

Trastuzumab IV

Ubicaciones

Hospital Britanico de Buenos Aires

Patrocinadores