A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer (APHINITY)

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer

Treatments: Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Trastuzumab; Drug: Doxorubicin; Drug: Pertuzumab; Drug: Paclitaxel; Drug: Epirubicin; Drug: Placebo; Drug: Carboplatin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01358877

2010-022902-41 (EudraCT Number)

BO25126

TOC4939G (Other Identifier)

BIG 4-11 (Other Identifier)

Details and patient eligibility

About

This randomized, double-blind, placebo-controlled, two-arm study will assess the safety and efficacy of pertuzumab in addition to chemotherapy plus trastuzumab as adjuvant therapy in participants with operable HER2-positive primary breast cancer. This study will be carried out in collaboration with the Breast International Group (BIG).

Enrollment: 4,804 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is histologically confirmed, and adequately excised
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1
• Known hormone receptor status (estrogen receptor and progesterone receptor)
• The interval between definitive surgery for breast cancer and the first dose of chemotherapy must be no more than 8 weeks (56 days). The first cycle of chemotherapy must be administered within 7 days of randomization or on Day 56, whichever occurs first
• Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55 percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
• Confirmed HER2 positive status
• Completion of all necessary baseline laboratory and radiologic investigations prior to randomization
• Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the participant and/or partner for the duration of the study treatment and for at least 7 months after the last dose of study drug

Exclusion criteria

• History of any prior (ipsi- and/or contralateral) invasive breast cancer
• History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin
• Any "clinical" T4 tumor as defined by primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer
• Any node-negative tumor
• Any previous systemic chemotherapy for cancer or radiotherapy for cancer
• Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer
• Concurrent anti-cancer treatment in another investigational trial
• Serious cardiac or cardiovascular disease or condition
• Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness
• Abnormal laboratory tests immediately prior to randomization
• Pregnant or lactating women
• Sensitivity to any of the study medications or any of the ingredients or excipients of these medications

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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4,804 participants in 2 patient groups, including a placebo group

Pertuzumab + Trastuzumab + Chemotherapy

Experimental group

Description:

Participants will receive pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m\^2 + epirubicin 90-120 mg/m\^2 or doxorubicin 50 mg/m\^2 + cyclophosphamide 500-600 mg/m\^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m\^2 for 3 cycles, 75 mg/m\^2 in first cycle and 100 mg/m\^2 in subsequent cycles, or 75 mg/m\^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m\^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m\^2 or epirubicin 90-120 mg/m\^2 + cyclophosphamide 500-600 mg/m\^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m\^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).

Treatment:

Drug: Carboplatin

Drug: Epirubicin

Drug: Paclitaxel

Drug: Pertuzumab

Drug: Doxorubicin

Drug: Trastuzumab

Drug: Docetaxel

Drug: Cyclophosphamide

Drug: 5-Fluorouracil

Placebo + Trastuzumab + Chemotherapy

Placebo Comparator group

Description:

Participants will receive placebo matching to pertuzumab IV Q3W and trastuzumab (8 milligrams per kilogram \[mg/kg\] loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 milligrams per square meter (mg/m\^2) + epirubicin 90-120 mg/m\^2 or doxorubicin 50 mg/m\^2 + cyclophosphamide 500-600 mg/m\^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m\^2 for 3 cycles, 75 mg/m\^2 in first cycle and 100 mg/m\^2 in subsequent cycles, or 75 mg/m\^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m\^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m\^2 or epirubicin 90-120 mg/m\^2 + cyclophosphamide 500-600 mg/m\^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m\^2 + carboplatin AUC 6 (up to 900 milligrams \[mg\]).

Treatment:

Drug: Placebo

Drug: Carboplatin

Drug: Epirubicin

Drug: Paclitaxel

Drug: Doxorubicin

Drug: Trastuzumab

Drug: Docetaxel

Drug: Cyclophosphamide

Drug: 5-Fluorouracil