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A Study of Everolimus Plus Exemestane in Chinese Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Non-steroidal Aromatase Inhibitor (BOLERO-5)

Primary Purpose

Advanced Breast Cancer

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Everolimus
Exemestane
Everolimus Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Breast Cancer focused on measuring everolimus, exemestane, advanced Breast Cancer, non-steroidal aromatase inhibitors, breast carcinoma, breast cancer, breast lump, HER2 negative, breast cancer progression

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

locally advanced, recurrent, or metastatic breast cancer. Locally advanced breast cancer must not be amenable to curative treatment by surgery or radiotherapy.

  • Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer

  • Postmenopausal women. Postmenopausal status is defined either by:

    • Prior bilateral oophorectomy
    • Or age ≥60
    • Or age < 60 and amenorrhea for 12 or more months

  • Recurrence or progression on prior NSAI is defined as:

    • Recurrence while on, or within one year (12 months) of end of adjuvant treatment with letrozole or anastrozole OR
    • Progression while on or within one month (30 days) of the end of prior treatment with letrozole or anastrozole
  • Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment

  • Patient must have as per RECIST 1.1

    • measurable disease or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.

    8. Patient is able to swallow and retain oral medication 9. Patient must meet the hematologic & biochemistery laboratory values at the screening visit:

  • Written informed consent must be obtained prior to any screening procedures

Exclusion Criteria:

  • Patients eligible for this study must not meet any of the following criteria:
  • HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test. Note: Patients with IHC 2+ must have a negative in situ hybridization test.
  • Patients who received more than one chemotherapy line for ABC
  • Patient with symptomatic visceral disease and is candidate to chemotherapy
  • Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis (e.g. pleural effusion, ascites etc.)
  • Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except topical applications, inhaled sprays, eye drops or local injections.
  • Uncontrolled diabetes mellitus as defined by HbA1c >7% despite adequate therapy.

Other protocol-defined inclusion/exclusion criteria may apply"

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Everolimus + Exemestane

Placebo + Exemestane

Arm Description

Everolimus 10mg/Day + Exemestane 25mg/Day

Placebo of everolimus in combination with exemestane 25 mg daily

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. PFS will be analyzed when approximately 110 events are reached.

Secondary Outcome Measures

Progression-free Survival (PFS) assessed by Blinded Independent Review Committee (BIRC).
PFS in the two treatment arms as determined by a Blinded Independent Review Committee (BIRC).
Overall survival
Overall survival (OS) in the two treatment arms
Overall response rate (ORR)
Overall response rate (ORR) defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR). ORR will be analysed when approximatly 110 events are reached.
Clinical benefit rate (CBR)
CBR, defined as the proportion of patients with best overall response of complete response (CR), partial response (PR) or stable disease (SD) with duration of 24 weeks or longer. CBR will be analyzed when approximately 110 events are reached.
Time to response
Time to response, defined as the time between date of randomization until first documented response (CR or PR). it will be analyzed when approximately 110 events are reached.
Duration of Response DOR
DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause
ECOG
Time to deterioration of ECOG Performance Status

Full Information

First Posted
September 15, 2017
Last Updated
June 17, 2022
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03312738
Brief Title
A Study of Everolimus Plus Exemestane in Chinese Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Non-steroidal Aromatase Inhibitor
Acronym
BOLERO-5
Official Title
A Randomized, Double-blind, Placebo Controlled, Phase II Study of Everolimus in Combination With Exemestane in the Treatment of Chinese Postmenopausal Women With Estrogen Receptor Positive, HER-2 Negative, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
September 15, 2017 (Actual)
Primary Completion Date
May 19, 2020 (Actual)
Study Completion Date
April 25, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study aims at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- ABC after recurrence or progression on letrozole or anastrozole. The rationale of this study is based on the following: Proven everolimus activity in breast cancer in combination with exemestane Efficacy and manageable safety profile of everolimus in combination with exemestane in the Asian subpopulation of BOLERO-2

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Breast Cancer
Keywords
everolimus, exemestane, advanced Breast Cancer, non-steroidal aromatase inhibitors, breast carcinoma, breast cancer, breast lump, HER2 negative, breast cancer progression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
this is a double-blind, randomized, placebo-controlled study, parallel groups,
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
double blinded study
Allocation
Randomized
Enrollment
159 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus + Exemestane
Arm Type
Experimental
Arm Description
Everolimus 10mg/Day + Exemestane 25mg/Day
Arm Title
Placebo + Exemestane
Arm Type
Active Comparator
Arm Description
Placebo of everolimus in combination with exemestane 25 mg daily
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Everolimus was formulated as tablets of 5-mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) are administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.
Intervention Type
Drug
Intervention Name(s)
Exemestane
Intervention Description
Exemestane 25 mg orally daily.
Intervention Type
Drug
Intervention Name(s)
Everolimus Placebo
Intervention Description
Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) are administered in a blinded manner on their respective treatment arms by continuous oral daily dosing.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. PFS will be analyzed when approximately 110 events are reached.
Time Frame
date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months.
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS) assessed by Blinded Independent Review Committee (BIRC).
Description
PFS in the two treatment arms as determined by a Blinded Independent Review Committee (BIRC).
Time Frame
date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months.
Title
Overall survival
Description
Overall survival (OS) in the two treatment arms
Time Frame
date of randomization to date of death up to approximately 19 months
Title
Overall response rate (ORR)
Description
Overall response rate (ORR) defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR). ORR will be analysed when approximatly 110 events are reached.
Time Frame
date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months.
Title
Clinical benefit rate (CBR)
Description
CBR, defined as the proportion of patients with best overall response of complete response (CR), partial response (PR) or stable disease (SD) with duration of 24 weeks or longer. CBR will be analyzed when approximately 110 events are reached.
Time Frame
date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months
Title
Time to response
Description
Time to response, defined as the time between date of randomization until first documented response (CR or PR). it will be analyzed when approximately 110 events are reached.
Time Frame
date of randomization to the date of the first documented progression or death from any cause which ever occur first, up to approximatly 19 months.
Title
Duration of Response DOR
Description
DOR, defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause
Time Frame
date of first documented CR or PR to date of first documented disease progression or death due to any cause up to apprximately 19 months
Title
ECOG
Description
Time to deterioration of ECOG Performance Status
Time Frame
date of randomization up to approximately 19 months
Other Pre-specified Outcome Measures:
Title
Pharmacokinetics of everolimus (Cmin)
Description
Characterize the pharmacokinetics of everolimus (Cmin, C2h) when administered
Time Frame
predose, two hours post dose

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: locally advanced, recurrent, or metastatic breast cancer. Locally advanced breast cancer must not be amenable to curative treatment by surgery or radiotherapy. Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer Postmenopausal women. Postmenopausal status is defined either by: Prior bilateral oophorectomy Or age ≥60 Or age < 60 and amenorrhea for 12 or more months Recurrence or progression on prior NSAI is defined as: Recurrence while on, or within one year (12 months) of end of adjuvant treatment with letrozole or anastrozole OR Progression while on or within one month (30 days) of the end of prior treatment with letrozole or anastrozole Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment Patient must have as per RECIST 1.1 • measurable disease or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease. 8. Patient is able to swallow and retain oral medication 9. Patient must meet the hematologic & biochemistery laboratory values at the screening visit: Written informed consent must be obtained prior to any screening procedures Exclusion Criteria: Patients eligible for this study must not meet any of the following criteria: HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test. Note: Patients with IHC 2+ must have a negative in situ hybridization test. Patients who received more than one chemotherapy line for ABC Patient with symptomatic visceral disease and is candidate to chemotherapy Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis (e.g. pleural effusion, ascites etc.) Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except topical applications, inhaled sprays, eye drops or local injections. Uncontrolled diabetes mellitus as defined by HbA1c >7% despite adequate therapy. Other protocol-defined inclusion/exclusion criteria may apply"
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
Novartis Investigative Site
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
150081
Country
China
Facility Name
Novartis Investigative Site
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610072
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100036
Country
China
Facility Name
Novartis Investigative Site
City
Chongqing
ZIP/Postal Code
400016
Country
China
Facility Name
Novartis Investigative Site
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Facility Name
Novartis Investigative Site
City
Qingdao
ZIP/Postal Code
266000
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Novartis Investigative Site
City
Wuhan
ZIP/Postal Code
430000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

A Study of Everolimus Plus Exemestane in Chinese Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Non-steroidal Aromatase Inhibitor

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