BOLERO-5: 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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03312738

Collaborator

(none)

159

Enrollment

Locations

Arms

55.3

Actual Duration (Months)

10.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer	Drug: Everolimus Drug: Exemestane Drug: Everolimus Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

159 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

this is a double-blind, randomized, placebo-controlled study, parallel groups,this is a double-blind, randomized, placebo-controlled study, parallel groups,

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

double blinded study

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 15, 2017

Actual Primary Completion Date :

May 19, 2020

Actual Study Completion Date :

Apr 25, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Everolimus + Exemestane Everolimus 10mg/Day + Exemestane 25mg/Day	Drug: Everolimus 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. Other Names: RAD001 Drug: Exemestane Exemestane 25 mg orally daily.
Active Comparator: Placebo + Exemestane Placebo of everolimus in combination with exemestane 25 mg daily	Drug: Exemestane Exemestane 25 mg orally daily. Drug: Everolimus Placebo 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.

Arm

Intervention/Treatment

Experimental: Everolimus + Exemestane

Everolimus 10mg/Day + Exemestane 25mg/Day

Drug: Everolimus

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.

Other Names:

RAD001

Drug: Exemestane

Exemestane 25 mg orally daily.

Active Comparator: Placebo + Exemestane

Placebo of everolimus in combination with exemestane 25 mg daily

Drug: Exemestane

Exemestane 25 mg orally daily.

Drug: Everolimus Placebo

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.

Outcome Measures

Primary Outcome Measures

Progression-free Survival (PFS) [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.]
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). [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.]
PFS in the two treatment arms as determined by a Blinded Independent Review Committee (BIRC).
Overall survival [date of randomization to date of death up to approximately 19 months]
Overall survival (OS) in the two treatment arms
Overall response rate (ORR) [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.]
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) [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]
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 [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.]
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 [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]
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 [date of randomization up to approximately 19 months]
Time to deterioration of ECOG Performance Status

Other Outcome Measures

Pharmacokinetics of everolimus (Cmin) [predose, two hours post dose]
Characterize the pharmacokinetics of everolimus (Cmin, C2h) when administered

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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.

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"

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Guangzhou	Guangdong	China	510000
2	Novartis Investigative Site	Harbin	Heilongjiang	China	150081
3	Novartis Investigative Site	Wuhan	Hubei	China	430022
4	Novartis Investigative Site	Nanjing	Jiangsu	China	210009
5	Novartis Investigative Site	Shanghai	Shanghai	China	200032
6	Novartis Investigative Site	Chengdu	Sichuan	China	610041
7	Novartis Investigative Site	Chengdu	Sichuan	China	610072
8	Novartis Investigative Site	Tianjin	Tianjin	China	300060
9	Novartis Investigative Site	Hangzhou	Zhejiang	China	310022
10	Novartis Investigative Site	Beijing		China	100036
11	Novartis Investigative Site	Chongqing		China	400016
12	Novartis Investigative Site	Guangzhou		China	510060
13	Novartis Investigative Site	Qingdao		China	266000
14	Novartis Investigative Site	Shanghai		China	200025
15	Novartis Investigative Site	Wuhan		China	430000