Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer (BOLERO-3)

Novartis

Status and phase: Completed; Phase 3

Conditions: HER2/Neu Over-expressing Locally Advanced Breast Cancer; Metastatic Breast Cancer

Treatments: Drug: trastuzumab; Drug: vinorelbine; Drug: Placebo; Drug: everolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT01007942

2008-008697-31 (EudraCT Number)

CRAD001W2301

Details and patient eligibility

About

This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane.

Enrollment: 569 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
• HER2+ status defined as IHC 3+ staining or in situ hybridization positive
• Patients with resistance to trastuzumab
• Prior taxane therapy
• Patients with an ECOG performance status of 0 - 2
• Patients with measurable disease as per RECIST criteria
• Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
• Patients must meet laboratory criteria defined in the study within 21 days prior to randomization

Exclusion criteria

• Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
• More than three prior chemotherapy lines for advanced disease.
• Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
• Peripheral neuropathy ≥ grade 2 at randomization
• Active cardiac disease
• History of cardiac dysfunction
• Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
• Known hypersensitivity to any study medication
• Breastfeeding or pregnant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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569 participants in 2 patient groups, including a placebo group

Everolimus + vinorelbine + trastuzumab

Experimental group

Description:

Oral everolimus (5 mg/day) + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)

Treatment:

Drug: trastuzumab

Drug: everolimus

Drug: vinorelbine

placebo + vinorelbine + trastuzumab

Placebo Comparator group

Description:

Oral daily matching placebo + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only

Treatment:

Drug: trastuzumab

Drug: vinorelbine

Drug: Placebo