Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer (BOLERO-1)

Novartis

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Paclitaxel; Drug: Trastuzumab; Drug: Placebo; Drug: Everolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT00876395

2008-006556-21 (EudraCT Number)

CRAD001J2301

Details and patient eligibility

About

The purpose of this Phase III study was to confirm the value of adding everolimus to weekly paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.

Enrollment: 719 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult Women (≥ 18 years old).
• Histologically or cytologically confirmed invasive breast carcinoma with local recurrence or radiological evidence of metastatic disease.
• Must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease.
• HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is allowed but should be discontinued > 12 months prior to randomization.
• Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment.
• Documentation of negative pregnancy test.
• Organ functions at time of inclusion.

Exclusion criteria

• Prior mTOR inhibitors for the treatment of cancer.
• Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.
• Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites, etc).
• Radiotherapy to ≥ 25% of the bone marrow within 4 weeks prior to randomization
• History of central nervous system metastasis.
• Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the upper gastrointestinal tract.
• Serious peripheral neuropathy.
• Cardiac disease or dysfunction.
• Uncontrolled hypertension.
• HIV.
• Pregnant,

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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719 participants in 2 patient groups, including a placebo group

Everolimus + Paclitaxel + Trastuzumab

Experimental group

Description:

Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22

Treatment:

Drug: Everolimus

Drug: Paclitaxel

Drug: Trastuzumab

Placebo + Paclitaxel + Trastuzumab

Placebo Comparator group

Description:

Placebo of everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22

Treatment:

Drug: Placebo

Drug: Paclitaxel

Drug: Trastuzumab