NCT01698918|CompletedPhase 2ResultsFDA Drug

Open-label, Phase II, Study of Everolimus Plus Letrozole in Postmenopausal Women With ER+, HER2- Metastatic or Locally Advanced Breast Cancer

BOLERO-4

An Open-label, Phase II, Single-arm Study of Everolimus in Combination With Letrozole in the Treatment of Postmenopausal Women With Estrogen Receptor Positive HER2 Negative Metastatic or Locally Advanced Breast Cancer

Novartis Pharmaceuticals ClinicalTrials.gov

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2 other identifiers

CRAD001Y241352012-003065-17

Study Type

interventional

Target

202

Locations

13 countries

Sites

Timeline

RegisteredOct 2012

StartedMar 2013

CompletionJan 2021

Brief Summary

The purpose of this study was to assess the efficacy and safety of first-line treatment with everolimus plus letrozole in postmenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer. Moreover, the study also aimed to investigate the efficacy and safety of second line treatment with everolumus plus examestane in participants whose disease progressed during everolimus plus letrozole therapy.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

202

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Mar 2013

Longer than P75 for phase_2

Geographic Reach

13 countries

52 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.9 years study duration

First Submitted

Initial submission to the registry

October 1, 2012

Completed

2 days until next milestone

First Posted

Study publicly available on registry

October 3, 2012

Completed

5 months until next milestone

Study Start

First participant enrolled

March 7, 2013

Completed

2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 17, 2015

Completed

5.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 13, 2021

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

February 9, 2022

Completed

Last Updated

May 3, 2023

Status Verified

April 1, 2023

Enrollment Period

2.8 years

First QC Date

October 1, 2012

Results QC Date

January 12, 2022

Last Update Submit

April 28, 2023

Conditions

Hormone Receptor Positive Breast Cancer

Keywords

Metastatic breast cancerLocally advanced breast cancerHER2-ER+EverolimusAfinitor

Outcome Measures

Primary Outcomes (1)

First-line Treatment: Progression-free Survival (PFS)
PFS in the first line setting is defined as the time from the date of enrollment to the date of first documented progression based on local radiology review or death due to any cause. If a participant did not progress or was not known to have died at the date of the analysis cut-off or start of another antineoplastic therapy, the PFS date was censored to the date of last adequate tumor assessment prior to cut-off date or start of antineoplastic therapy. The median PFS was estimated and presented along with 95% confidence intervals. The primary analysis of PFS for first line was performed 12 months after the last patient's recruitment.
From the date of enrollment to the date of first documented progression or deaths, assessed up to approximately 2.8 years

Secondary Outcomes (21)

First-line Treatment: Overall Response Rate (ORR)
From the date of enrollment until discontinuation of first-line treatment, assessed up to approximately 3.8 years
First-line Treatment: Clinical Benefit Rate (CBR)
From the date of enrollment until first-line treatment discontinuation, assessed up to approximately 3.8 years
Second-line Treatment: Progression-free Survival (PFS)
From the start of the second-line treatment until the date of first documented progression or death, assessed up to approximately 2.4 years
Second-line Treatment: Overall Response Rate (ORR)
From the start of the second-line treatment up to approximately 2.4 years
Second-line Treatment: Clinical Benefit Rate (CBR)
From the start of the second-line treatment up to approximately 2.4 years
+16 more secondary outcomes

Study Arms (1)

Everolimus+letrozole/exemestane (first line and second line treatment)

EXPERIMENTAL

Participants received everolimus in combination with letrozole as first-line treatment. Only participants who had disease progression in the first line setting (core phase) were offered second-line treatment (everolimus in combination with exemestane)

Drug: EverolimusDrug: LetrozoleDrug: ExemestaneDrug: Alcohol-free dexamethasone mouth rinse (Stomatitis sub-study)Drug: Standard of care to treat stomatitis (Stomatitis sub-study)

Interventions

EverolimusDRUG

Everolimus was self-administered as a daily dose of 10mg (two 5mg tablets) taken orally continuously until progression of disease, unacceptable toxicity or withdrawal of consent.

Also known as: RAD001