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

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: November 2, 2009
Last updated: October 13, 2015
Last verified: October 2015
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.

Condition Intervention Phase
HER2/Neu Over-expressing Locally Advanced Breast Cancer
Metastatic Breast Cancer
Drug: everolimus, vinorelbine, trastuzumab
Drug: Placebo + vinorelbine + trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Phase III, Double-blind, Placebo-controlled Multicenter Trial of Daily Everolimus in Combination With Trastuzumab and Vinorelbine, in Pretreated Women With HER2/Neu Over-expressing Locally Advanced or Metastatic Breast Cancer.

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progressive-free survival (PFS), defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first. [ Time Frame: Every 6 months ]

Secondary Outcome Measures:
  • Overall survival (OS), defined as the time from date of randomization to the date of death from any cause. [ Time Frame: Every 3 months ]
  • Overall response rate (ORR) defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST [ Time Frame: Every 6 weeks ]
  • Patient reported outcome (PRO) questionnaires [ Time Frame: Every 6 weeks ]
  • Clinical benefit rate (CBR) defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks. [ Time Frame: Every 6 weeks ]
  • Laboratory assessments (hematology, chemistry, coagulation), AEs graded by CTCAE version 3.0 or equivalent [ Time Frame: Continuous until 28 days after the last dose of study drug ]

Enrollment: 570
Study Start Date: October 2009
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + vinorelbine + trastuzumab Drug: everolimus, vinorelbine, trastuzumab
Placebo Comparator: placebo + vinorelbine + trastuzumab Drug: Placebo + vinorelbine + trastuzumab


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Other protocol-defined inclusion/exclusion criteria may ap

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01007942

  Show 160 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals Identifier: NCT01007942     History of Changes
Other Study ID Numbers: CRAD001W2301
2008-008697-31 ( EudraCT Number )
Study First Received: November 2, 2009
Last Updated: October 13, 2015

Keywords provided by Novartis:
Metastatic breast cancer
locally advanced breast cancer
HER2/neu positive breast cancer
HER2/neu over-expressing
progressive-free survival (PFS)
over survival (OS)
bolero 3
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action processed this record on March 24, 2017