A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer

Roche

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Docetaxel; Drug: 5-Fluorouracil; Drug: Herceptin SC [trastuzumab]; Drug: Cyclophosphamide; Drug: Herceptin IV [trastuzumab]; Drug: Epirubicin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00950300

BO22227

2008-007326-19 (EudraCT Number)

Details and patient eligibility

About

In this open-label multicenter trial, participants with operable or locally advanced breast cancer will be randomized to pre-operative treatment with 8 cycles of chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide) concurrent with either SC Herceptin or IV Herceptin. After surgery, participants will receive a further 10 cycles of SC or IV Herceptin as per randomization to complete 1 year of treatment. All cycles will be 21 days in length. After the end of study treatment, participants will be followed for safety and efficacy for up to 5 years or until disease recurrence, whichever is earlier.

Enrollment: 596 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult women greater than or equal to (≥) 18 years of age
• Non-metastatic primary invasive adenocarcinoma of the breast clinical stage I to IIIC, including inflammatory and multicentric/multifocal breast cancer, with tumor size ≥1 centimeter (cm) by ultrasound or ≥2 cm by palpation, centrally confirmed HER2-positive (immunohistochemical score [IHC] 3+ or in situ hybridization [ISH]-positive)
• At least 1 measurable lesion in breast or lymph nodes (≥1 cm by ultrasound or ≥2 cm by palpation), except for inflammatory carcinoma (T4d)
• Baseline left ventricular ejection fraction (LVEF) ≥55%
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
• Adequate organ function at Baseline

Exclusion criteria

• History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
• Past or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and in situ carcinoma of the cervix
• Metastatic disease
• Any prior therapy with anthracyclines
• Prior anti-HER2 therapy or biologic or immunotherapy
• Serious cardiac illness
• Pregnant or lactating women

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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596 participants in 2 patient groups

Herceptin IV + Chemotherapy

Active Comparator group

Description:

Participants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.

Treatment:

Drug: Docetaxel

Drug: Herceptin IV [trastuzumab]

Drug: Epirubicin

Drug: 5-Fluorouracil

Drug: Cyclophosphamide

Herceptin SC + Chemotherapy

Experimental group

Description:

Participants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.

Treatment:

Drug: Docetaxel

Drug: Epirubicin

Drug: 5-Fluorouracil

Drug: Cyclophosphamide

Drug: Herceptin SC [trastuzumab]