Overview

A Study to Evaluate Patient Preference for Home Administration of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration in Participants With Early or Locally Advanced/Inflammatory HER2-Positive Breast Cancer

Status:
Not yet recruiting
Trial end date:
2025-09-25
Target enrollment:
0
Participant gender:
All
Summary
This is a Phase IIIb, multinational, multicenter, randomized, open-label study to evaluate patient preference of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous use (PH FDC SC) administration in the home setting compared with the hospital setting during the cross-over period of adjuvant treatment in participants with early or locally advanced/inflammatory human epidermal growth factor receptor 2-positive (HER2+) breast cancer.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hoffmann-La Roche
Treatments:
Ado-Trastuzumab Emtansine
Maytansine
Pertuzumab
Trastuzumab
Criteria
Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Intact skin at planned site of subcutaneous (SC) injections

- Left ventricular ejection fraction (LVEF) greater than or equal to (≥)55% by
echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)

- Negative human immunodeficiency virus (HIV) test at screening

- Negative hepatitis B surface antigen (HBsAg) test at screening

- Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at
screening accompanied by either of the following: Negative total hepatitis B core
antibody (HBcAb); Positive total HBcAb test followed by a negative (per local
laboratory definition) hepatitis B virus (HBV) DNA test

- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
test followed by a negative HCV RNA test at screening

- For female participants of childbearing potential: agreement to remain abstinent or
use contraception and agree to refrain from donating eggs during the treatment period
and for 7 months after the final dose of the study treatment

- For male participants: agreement to remain abstinent or use a condom, and agree to
refrain from donating sperm during the treatment period and for 7 months after the
final dose of study treatment

Disease-specific Inclusion Criteria:

- Female and male participants with stage II-IIIC early or locally advanced/inflammatory
human epidermal growth factor receptor 2-positive (HER2+) breast cancer

- Primary tumor >2 centimetres (cm) in diameter, or node-positive disease

- HER2+ breast cancer confirmed by a local laboratory prior to study enrollment. HER2+
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) following American Society of Clinical Oncology (ASCO)/College of
American Pathologists (CAP) guidelines 2018 and updates (Wolff et al. Arch Pathol Lab
Med 2018)

- Hormone receptor status of the primary tumor determined by local assessment following
American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP)
guidelines and updates (Allison et al. J Clin Oncol 2020)

- Agreement to undergo mastectomy or breast conserving surgery after neoadjuvant
therapy, including the axillary nodes

- Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for local
confirmation of HER2 and hormone receptor status following current ASCO/CAP guidelines

Inclusion Criteria for Treatment with Adjuvant PH FDC SC:

- Completed the neoadjuvant phase of this study and underwent surgery, and achieved
pathologic complete response (pCR), defined as eradication of invasive disease in the
breast and axilla according to the current American Joint Committee on Cancer (AJCC)
staging system classification, and using the resected specimen by the local
pathologist on the basis of guidelines to be provided in a pathology manual

- Adequate wound healing after breast cancer surgery per investigator's assessment to
allow initiation of study treatment within less than or equal to (≤)9 weeks of last
systemic neoadjuvant therapy

Exclusion Criteria:

- Stage IV (metastatic) 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. A participant with previous invasive non-breast
cancer is eligible provided he/she has been disease free for more than 5 years

- Participants who are pregnant or breastfeeding or intending to become pregnant during
the study or within 7 months after the final dose of study treatments

- Treatment with investigational therapy within 28 days prior to initiation of study
treatment

- Active, unresolved infections at screening requiring treatment

- Participants who may have had a recent episode of thromboembolism and are still trying
to optimize the anticoagulation dose and/or have not normalized their International
Normalized Ratio (INR)

- Serious cardiac illness or medical conditions

- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias

- Inadequate bone marrow function

- Impaired liver function

- Renal function with creatinine clearance <50 mL/min using the Cockroft-Gault formula
and serum creatinine >1.5x upper limit of normal (ULN)

- Major surgical procedure unrelated to breast cancer within 28 days prior to study
entry or anticipation of the need for major surgery during the course of study
treatment

- Current severe, uncontrolled systemic disease that may interfere with planned
treatment

- Any serious medical condition or abnormality in clinical laboratory tests that
precludes an individual'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

- Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins
or a history of severe allergic or immunological reactions, e.g., difficult to control
asthma

- Current chronic daily treatment with corticosteroids

- Assessment by the investigator as being unable or unwilling to comply with the
requirements of the protocol

Cancer-specific Exclusion Criteria for Neoadjuvant Phase:

- Participants who have received any previous systemic therapy for treatment or
prevention of breast cancer, or radiation therapy for the treatment of cancer

- Participants who 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 ipsi- or contralateral breast cancer

- Participants with high-risk for breast cancer who have received chemopreventive drugs
in the past

- Participants with multicentric breast cancer, unless all tumors are HER2+

- Participants with bilateral breast cancer

- Participants who 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

Exclusion Criterion for Treatment with Adjuvant Trastuzumab Emtansine (Arm E):

- Current Grade ≥3 peripheral neuropathy (according to the NCI CTCAE v5.0)