A Study of Pertuzumab in Combination With Herceptin and Chemotherapy in Participants With HER2-Positive Breast Cancer

Roche

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Trastuzumab; Drug: FEC; Drug: Docetaxel; Drug: Pertuzumab; Drug: TCH

Study type: Interventional

Funder types: Industry

Identifiers

NCT00976989

BO22280

2009-012019-17 (EudraCT Number)

Details and patient eligibility

About

This 3 arm study will assess the tolerability, safety and efficacy of 3 neoadjuvant treatment regimens in participants with locally advanced, inflammatory or early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Before surgery, participants will be randomized to receive either A) 6 cycles of pertuzumab plus trastuzumab (Herceptin), with 5-fluorouracil/epirubicin/cyclophosphamide (FEC) for cycles 1-3 and docetaxel for cycles 4-6, or B) FEC for cycles 1-3 followed by pertuzumab plus trastuzumab with docetaxel for cycles 4-6, or C) 6 cycles of pertuzumab plus trastuzumab with docetaxel and carboplatin. Pertuzumab will be administered at a loading dose of 840 mg intravenously (iv), then 420 mg iv 3-weekly, trastuzumab at a loading dose of 8 mg/kg iv, then 6 mg/kg iv 3-weekly, docetaxel at 75 mg/m^2 iv, increased to 100 mg/m^2 iv 3-weekly, and FEC and carboplatin iv 3-weekly at standard doses. Following surgery participants will receive trastuzumab 6 mg/kg iv 3-weekly for a total of 1 year, as well as adequate chemo-, radio- and hormone therapy. Anticipated time on study treatment is 4-12 months, and target sample size is 200-300.

Enrollment: 225 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• female participants, age >/=18 years
• advanced, inflammatory or early stage unilateral invasive breast cancer
• HER2-positive breast cancer
• baseline left ventricular ejection fraction (LVEF) >/=55%

Exclusion criteria

• metastatic disease (Stage IV) or bilateral breast cancer
• previous anticancer therapy or radiotherapy for any malignancy
• other malignancy, except for carcinoma in situ of the cervix, or basal cell carcinoma
• clinically relevant cardiovascular disease
• current chronic treatment with corticosteroids of >10mg methylprednisolone or equivalent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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225 participants in 3 patient groups

T+P Concomitant Anthracycline-based chemotherapy

Experimental group

Description:

5-Fluorouracil, epirubicin with cyclophosphamide (FEC), trastuzumab (T) and pertuzumab (P) every three weeks for three cycles, followed by docetaxel, trastuzumab and pertuzumab every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.

Treatment:

Drug: Pertuzumab

Drug: FEC

Drug: Docetaxel

Drug: Trastuzumab

T+P Sequential Anthracycline-based chemotherapy

Experimental group

Description:

FEC every three weeks for three cycles, followed by docetaxel, trastuzumab (T) and pertuzumab (P) every three weeks, for three cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 21 as adjuvant therapy post-surgery.

Treatment:

Drug: Pertuzumab

Drug: FEC

Drug: Docetaxel

Drug: Trastuzumab

T+P Concomitant Non-Anthracycline chemotherapy

Experimental group

Description:

Trastuzumab, carboplatin, docetaxel (TCH) and pertuzumab (P) every three weeks, for six cycles as neoadjuvant therapy. Trastuzumab every three weeks from Cycle 7 up to Cycle 17 as adjuvant therapy post-surgery.

Treatment:

Drug: Pertuzumab

Drug: TCH