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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: November 2, 2009
Last updated: May 30, 2013
Last verified: May 2013

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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Patient reported outcome (PRO) questionnaires [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 570
Study Start Date: October 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (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
Genders 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01007942

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

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01007942     History of Changes
Other Study ID Numbers: CRAD001W2301, 2008-008697-31
Study First Received: November 2, 2009
Last Updated: May 30, 2013
Health Authority: United States: Food and Drug Administration

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
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014