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NCT01007942 · CITED IN SOURCE DOCUMENTS

Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2017-04-05

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progressive-free Survival (PFS) Per Investigator Assessment

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Clinical Benefit Rate (CBR)

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outcome · POSTED

Median Time to Deterioration of the ECOG Performance Status Score

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outcome · POSTED

PRO: Time to Deterioration in Global Health Status/QoL Domain Score of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) (by at Least 10%)

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outcome · POSTED

Everolimus Blood Concentrations by Leading Dose and Time Point

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outcome · POSTED

Vinorelbine Blood Concentrations by Leading Dose and Time Point

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outcome · POSTED

Trastuzumab Blood Concentrations by Leading Dose and Time Point

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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
healthy Volunteers
false
minimum Age
18 Years
sex
FEMALE
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. 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)
    intervention Names
    1. Drug: everolimus
    2. Drug: vinorelbine
    3. Drug: trastuzumab
    label
    Everolimus + vinorelbine + trastuzumab
    type
    EXPERIMENTAL
  2. 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
    intervention Names
    1. Drug: Placebo
    2. Drug: vinorelbine
    3. Drug: trastuzumab
    label
    placebo + vinorelbine + trastuzumab
    type
    PLACEBO_COMPARATOR
interventions
  1. arm Group Labels
    1. Everolimus + vinorelbine + trastuzumab
    description
    Oral everolimus was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.
    name
    everolimus
    other Names
    1. RAD001
    type
    DRUG
  2. arm Group Labels
    1. placebo + vinorelbine + trastuzumab
    description
    Oral everolimus placebo was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.
    name
    Placebo
    type
    DRUG
  3. arm Group Labels
    1. Everolimus + vinorelbine + trastuzumab
    2. placebo + vinorelbine + trastuzumab
    description
    intravenous vinorelbine (25 mg/m2 weekly)
    name
    vinorelbine
    type
    DRUG
  4. arm Group Labels
    1. Everolimus + vinorelbine + trastuzumab
    2. placebo + vinorelbine + trastuzumab
    description
    intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)
    name
    trastuzumab
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
DOUBLE
who Masked
  1. PARTICIPANT
  2. INVESTIGATOR
primary Purpose
TREATMENT
Enrollment
count
569
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    PFS was 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. PFS primary analysis performed when 415 events were reached. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    measure
    Progressive-free Survival (PFS) Per Investigator Assessment
    time Frame
    Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
secondary Outcomes
  1. description
    OS was defined as the time from date of randomization to the date of death from any cause. Final OS was conducted when 388 deaths occurred.
    measure
    Overall Survival (OS)
    time Frame
    Every 3 months until death up to 41 months
  2. description
    ORR was defined as the percentage of participants whose best overall response was either complete response (CR) or partial response (PR) according to RECIST version 1.0. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
    measure
    Overall Response Rate (ORR)
    time Frame
    Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
  3. description
    CBR was defined as the percentage of participants whose best overall response, according to RECIST, was either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
    measure
    Clinical Benefit Rate (CBR)
    time Frame
    Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
  4. description
    Time to deterioration of ECOG performance status score was summarized at time of assessment. ECOG (Eastern Cooperative Oncology Group)performance scale is a standard criteria for measuring how treatment of cancer impacts their level of functioning in terms of their ability to care for themselves, daily activity, \& physical ability (walking, working, etc.). Scale score ranges from 0 to 5, 5 being the worst. ECOG scale index: 0 - Fully active, able to carry on all pre-disease performance without restriction. 1 - Restricted in physically strenuous activity but ambulatory \& able to carry out work of a light or sedentary nature, e.g., light housework, office work. 2 - Ambulatory \& capable of all self-care but unable to carry out any work activities. Up \& about more than 50% of waking hours. 3 - Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 5 - Dead
    measure
    Median Time to Deterioration of the ECOG Performance Status Score
    time Frame
    baseline, until disease progression or death up to about 41 months
  5. description
    PRO = patient reported outcomes; Time to deterioration (≥ 10% worsening from baseline), in the global health status of EORTC QLQ-C30 scale was done in the 3 functional scales (emotional, physical, \& social functioning \[EF, PF, \& SF\]). It contains 30 items \& is composed of multi-item scales \& single-item measures. These include 5 functional scales (physical, role, emotional, social \& cognitive functioning), 3 symptom scales (fatigue, pain, nausea, \& vomiting), a global health status/QoL scale, and 6 single items (dyspnea, diarrhea, constipation, anorexia, insomnia \& financial impact). Each of the multi-item scale includes a different set of items - no item occurs in more than 1 scale. Each item in the EORTC QLQ-C30 has 4 response categories (1=Not at all, 2= A little, 3= Quite a bit, 4= Very much) with the higher number representing a worse outcome. The global health domain score of the QLQ-C30 questionnaire was pre-specified as the primary QoL domain of interest \& disclosed here.
    measure
    PRO: Time to Deterioration in Global Health Status/QoL Domain Score of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) (by at Least 10%)
    time Frame
    Baseline, until disease progression or death up to about 41 months
  6. description
    Pre-dose (Cmin) and 2 hours post-dose (C2h) everolimus PK blood samples were collected at Cycle 2 Day 1. Only valid everolimus PK blood samples collected at steady state were used in the analyses.
    measure
    Everolimus Blood Concentrations by Leading Dose and Time Point
    time Frame
    Cycle 2, Day 1
  7. description
    Pre-infusion (Cmin) and end of infusion (C2h) vinorelbine PK blood samples were collected at Cycle 2 Day 1. Only valid vinorelbine PK blood samples collected at steady state were used in the analyses.
    measure
    Vinorelbine Blood Concentrations by Leading Dose and Time Point
    time Frame
    Cycle 2, Day 1
  8. description
    Pre-infusion (Cmin) and end of infusion (C2h) trastuzumab PK blood samples were collected at Cycle 3 Day 1. Only valid trastuzumab PK blood samples collected at steady state were used in the analyses.
    measure
    Trastuzumab Blood Concentrations by Leading Dose and Time Point
    time Frame
    Cycle 3, Day 1
Full study description
brief Summary
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.
Source references
references
  1. citation
    Andre F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. doi: 10.1016/S1470-2045(14)70138-X. Epub 2014 Apr 14.
    pmid
    24742739
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        x="-1">Evidence of mTOR inhibitor activity in HER2-positive breast cancer was shown in the double-blind, placebo-controlled, phase III <a href="/clinicaltrials/NCT01007942">BOLERO-3</a> trial (NCT01007942).[<a href="#cit/section_10.85">85</a>]</p> <div class="pdq-content-list"><ol id="_2542"><li>In the BOLERO-3 trial, 569
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      2. context exact
        activity in HER2-positive breast cancer was shown in the double-blind, placebo-controlled, phase III <a href="/clinicaltrials/NCT01007942">BOLERO-3</a> trial (NCT01007942).[<a href="#cit/section_10.85">85</a>]</p> <div class="pdq-content-list"><ol id="_2542"><li>In the BOLERO-3 trial, 569 patients with HER2-positive, tra
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      source title
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      source update dates
      1. context
        Updated: April 25, 2025
        datetime
        2025-04-25T12:00:00Z
        display
        April 25, 2025

    Preserved source evidence · Not medical advice