A Study of the Safety of Subcutaneously Administered Trastuzumab (Herceptin) in Participants With Early and Locally Advanced Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer (SCHEARLY)

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Docetaxel; Drug: Doxorubicin; Drug: Paclitaxel; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01940497

ML28879

2013-001161-16 (EudraCT Number)

Details and patient eligibility

About

This non-randomized, multicenter, open-label study will assess the safety and efficacy of subcutaneously administered trastuzumab in participants with early and locally advanced HER2-positive breast cancer in two sequential cohorts. First 120 participants will be treated with subcutaneous (SC) trastuzumab 600 milligrams (mg) vial (Cohort A) and the subsequent 120 participants will be treated with SC trastuzumab prefilled single use injection device (SID) (Cohort B). Participants from each cohort will receive neoadjuvant or adjuvant chemotherapy consisting of doxorubicin every 3 weeks (q3w) (1 cycle) for 4 cycles followed by paclitaxel weekly or docetaxel every 3 weeks (q3w) in combination with SC trastuzumab (600 mg) q3w for 4 cycles and a further 14 cycles of SC trastuzumab (600 mg) q3w alone. All participants will be followed up for 24 months after the last participant has received the last dose of study treatment, or earlier in case of withdrawal from the study, loss to follow-up or death.

Enrollment: 240 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast. Stage of disease: T1-4 (T describes size of tumour from 1 to 4), N0-3 (N describes nearby lymph nodes), M0 (M describes distant metastasis)
• HER2-positive disease immunohistochemistry (IHC) 3+ or in situ hybridization (ISH) positive
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Left ventricular ejection fraction (LVEF) of greater than or equal to (>=) 55 percent (%) measured by echocardiography (ECHO) or multiple gated acquisition (MUGA) scan prior to first dose of trastuzumab SC
• Intact skin at site of SC injection on the thigh

Exclusion criteria

• History of other malignancy, except for participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively treated malignancies, other than breast cancer, who have been disease-free for at least 5 years
• Severe dyspnea at rest or requiring supplementary oxygen therapy
• Concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
• Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented congestive heart failure (CHF), high-risk uncontrolled arrhythmias, angina pectoris requiring medication, clinically significant valvular disease, evidence of transmural infarction on electrocardiogram (ECG), diagnosed poorly controlled hypertension
• Known infection with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Pregnant or lactating women
• Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment, including hormonal therapy, bisphosphonate therapy and immunotherapy, within 28 days prior to the first dose of study treatment
• Known hypersensitivity to trastuzumab, murine proteins, to any of the excipients of Herceptin including hyaluronidase, or the adhesive of the SC device (for Cohort B), or a history of severe allergic or immunological reactions, for example, difficulty to control asthma
• Inadequate bone marrow, hepatic or renal function
• Hormonal treatment concomitant with chemotherapy (allowed in adjuvant phase with adjuvant trastuzumab SC)
• Pre-existing motor or sensory neuropathy of Grade greater than (>) 1
• Synchronous bilateral invasive breast cancer

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

Trastuzumab (Vial)

Experimental group

Description:

Participants will receive trastuzumab 600 mg SC using a vial q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone).

Treatment:

Drug: Trastuzumab

Drug: Paclitaxel

Drug: Doxorubicin

Drug: Docetaxel

Trastuzumab (SID)

Experimental group

Description:

Participants will receive trastuzumab 600 mg SC using SID q3w (1 cycle) for 1 year (4 cycles in combination with adjuvant or neoadjuvant chemotherapy \[consisting of doxorubicin, paclitaxel or docetaxel\] and 14 cycles administered alone).

Treatment:

Drug: Trastuzumab

Drug: Paclitaxel

Drug: Doxorubicin

Drug: Docetaxel