Advanced Breast CancerPhase 2BOLERO-5NCT03312738
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
A Phase 2 study testing Everolimus and Exemestane in people with Advanced Breast Cancer, run by Novartis Pharmaceuticals at 15 sites in China.
Trial summary
This study aimed at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer after recurrence or progression on letrozole or anastrozole. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- Everolimus and Exemestane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 159 participants
- Where
- 15 sitesChina
- Study dates
- 15 Sep 2017to 25 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chinese Postmenopausal women with ER+ HER2- 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 was defined either by:
- Prior bilateral oophorectomy
- Or age ≥60
- Or age < 60 and amenorrhea for 12 or more months
Show all 17Show fewer
- Recurrence or progression on prior NSAI was 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 had as per RECIST 1.1
- measurable disease or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
- non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
- Patient was able to swallow and retain oral medication
- Patient met the hematologic and biochemistery laboratory values at the screening visit
- Patient had a WHO performance status ≤2
- Written informed consent obtained prior to any screening procedures
Who cannot join
- HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test.
- Patients who had received more than one chemotherapy line for ABC
- Patients with symptomatic visceral disease and candidates 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 used 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
China15 sites
Novartis Investigative Site
Beijing, 100036
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Chengdu, Sichuan, 610072
Novartis Investigative Site
Chongqing, 400016
Novartis Investigative Site
Guangzhou, Guangdong, 510000
Novartis Investigative Site
Guangzhou, 510060
Novartis Investigative Site
Hangzhou, Zhejiang, 310022
Novartis Investigative Site
Harbin, Heilongjiang, 150081
Novartis Investigative Site
Nanjing, Jiangsu, 210009
Novartis Investigative Site
Qingdao, 266000
Novartis Investigative Site
Shanghai, Shanghai Municipality, 200032
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300060
Novartis Investigative Site
Wuhan, Hubei, 430022
Novartis Investigative Site
Wuhan, 430000
About this study
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
This study aimed at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer after recurrence or progression on letrozole or anastrozole.
Read the detailed description
This was a multicenter, double-blind, randomized, placebo-controlled, phase II study evaluating treatment with everolimus (10 mg daily) in combination with exemestane (25 mg daily) vs placebo in combination with exemestane (25 mg daily) in Chinese postmenopausal women with locally advanced, recurrent or metastatic ER+ HER2- breast cancer refractory to non-steroidal aromatase inhibitors.
Randomized participants started the study treatment at Cycle 1 Day 1, and were treated continuously until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from treatment for any other reason.
After end of treatment, all participants were followed up for safety up to 30 days after last dose of study treatment (exemestane and/or everolimus/placebo). All participants were followed for survival status at least every 3 months after treatment discontinuation unless they discontinued due to death, consent withdrawal or lost to follow-up
If a participants permanently discontinued study treatment for reasons other than disease progression, death, lost to follow-up, or withdrawal of consent to efficacy follow-up then they entered the post-treatment efficacy follow-up period until disease progression, death, lost to follow-up or withdrawal of consent for efficacy follow-up.
- Conditions
- Advanced Breast Cancer
- Being tested
- Everolimus, Exemestane, Everolimus Placebo
- Keywords
- everolimus, exemestane, advanced Breast Cancer, non-steroidal aromatase inhibitors, breast carcinoma, breast cancer, breast lump, HER2 negative, breast cancer progression
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001
Everolimus was formulated as tablets of 5 mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) was administered in a blinded manner by continuous oral daily dosing.
ExemestaneDrug
Commercially available exemestane was supplied as 25 mg tablets. Exemestane was administered as continuous oral daily dose of 25 mg tablets.
Everolimus PlaceboDrug
Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) was administered in a blinded manner by continuous oral daily dosing.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus + Exemestane | Experimental | Participants received everolimus as a continuous oral daily dose of 10 mg and exemestane as a continuous oral daily dose of 25 mg Receives: Drug: Everolimus; Drug: Exemestane |
| Placebo + Exemestane | Active comparator | Participants received placebo as a continuous oral daily dose and exemestane as a continuous oral daily dose of 25 mg Receives: Drug: Exemestane; Drug: Everolimus Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the local investigator's tumor assessment per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
Measured: From randomization up to date of first documented progression or death, assessed up to approximately 3.5 years
Secondary outcomes (16)
Progression-free Survival (PFS) Based on Blinded Independent Review Committee (BIRC) Assessment
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the BIRC tumor assessment per RECIST 1.1.
The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
Measured: From randomization up to date of first documented progression or death, assessed up to approximately 1.8 years
Overall Survival (OS)
OS was defined as the time from date of randomization to date of death due to any cause. If the participant was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cutoff date.
The distribution of OS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of OS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
Measured: From randomization to date of death, up to approximately 3.8 years
Overall Response Rate (ORR) Based on Local Radiology Review of Tumor Assessment
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR) according to RECIST using local radiologist's/investigator's tumor assessment. ORR was estimated and the exact binomial 90% CI was reported by treatment arm.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: Up to approximately 3.5 years
Overall Response Rate (ORR) Based on BIRC Assessment
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR) according to RECIST using BIRC assessment. ORR was estimated and the exact binomial 90% CI was reported by treatment arm.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: Up to approximately 1.8 years
Clinical Benefit Rate (CBR) Based on Local Radiology Review of Tumor Assessment
CBR was defined as the percentage of patients with best overall response of CR, PR or an overall lesion response of stable disease (SD) or Non-CR/Non-progressive disease with duration of 24 weeks or longer according to RECIST 1.1 using local radiologist's/investigator's tumor assessment. CBR was estimated and the exact binomial 90% CI was reported by treatment arm.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Measured: Up to approximately 3.5 years
Clinical Benefit Rate (CBR) Based on BIRC Assessment
CBR was defined as the percentage of patients with best overall response of CR, PR or an overall lesion response of stable disease (SD) or Non-CR/Non-progressive disease with duration of 24 weeks or longer according to RECIST 1.1 using BIRC assessment. CBR was estimated and the exact binomial 90% CI was reported by treatment arm.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Measured: Up to approximately 1.8 years
Time to Response (TTR) Based on Local Radiology Review of Tumor Assessment
TTR was defined as the time between date of randomization until first documented response (CR or PR) according to RECIST 1.1 using local radiologist's/investigator's tumor assessment.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: Up to approximately 3.5 years
Time to Response (TTR) Based on BIRC Assessment
TTR was defined as the time between date of randomization until first documented response (CR or PR) according to RECIST 1.1 using BIRC assessment.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: Up to approximately 1.8 years
Duration of Response (DOR) Based on Local Radiology Review of Tumor Assessment
DOR was 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, according to RECIST 1.1 using local radiologist's/investigator's tumor assessment.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 3.5 years
Duration of Response (DOR) Based on BIRC Assessment
DOR was 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, according to RECIST 1.1 using BIRC assessment.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measured: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 1.8 years
Time to Definitive Deterioration of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score From Baseline
ECOG PS is a measure of functional status with scores ranging from 0 (fully active) to 5 (dead). Deterioration was considered definitive if no improvements in the ECOG PS status were observed after an instance of deterioration. Death was considered as worsening of the ECOG PS if it occurred close to the last assessment, where "close" is defined as twice the planned period between two assessments. Participants who died after more than twice the planned period between two assessments were censored at the date of their last assessment before the cut-off. Participants receiving any further anticancer therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Participants that had not worsened were censored at the date of last assessment prior to cut off. Time to definitive deterioration was estimated using the Kaplan-Meier method.
Measured: From randomization up to definitive deterioration of the ECOG PS by one categotu of the score, assessed up to approximately 3.5 years
Everolimus Predose Concentration (Cmin)
Blood samples were collected to assess everolimus predose concentration (Cmin) at steady state at Cycle 1 Week 4 (any day during week 4). Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection.
Everolimus concentrations were determined in the whole blood by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The method has a lower limit of quantitation (LLOQ) of 0.3 ng/mL for everolimus. Values below the LLOQ were set to 0.
Measured: Predose on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Everolimus Concentration at 2 Hours Post Dose (C2h)
Blood samples were collected to assess everolimus concentration at 2 hours post dose (C2h) at steady state at Cycle 1 Week 4 (any day during week 4) Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection.
Everolimus concentrations were determined in the whole blood by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The method has a LLOQ of 0.3 ng/mL for everolimus. Values below the LLOQ were set to 0.
Measured: Two hours post everolimus administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Exemestane Predose Concentration (Cmin)
Blood samples were collected to assess exemestane predose concentration (Cmin) at steady state at Cycle 1 Week 4 (any day during week 4). Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection.
Exemestane concentrations were determined in the whole blood by a liquid chromatography with LC-MS/MS method. The method has a LLOQ of 20 pg/mL for exemestane. Values below the LLOQ were set to 0.
Measured: Predose of exemestane on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Exemestane Concentration at 2 Hours Post Dose (C2h)
Blood samples were collected to assess exemestane concentration at 2 hours post dose (C2h) at steady state at Cycle 1 Week 4 (any day during week 4) Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection.
Exemestane concentrations were determined in the whole blood by a liquid chromatography with LC-MS/MS method. The method has a LLOQ of 20 pg/mL for exemestane. Values below the LLOQ were set to 0.
Measured: Two hours post exemestane administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Estradiol Levels After 4 Weeks of Study Treatment
Blood samples were collected to assess estradiol levels after 4 weeks of study treatment. Estradiol was determined in plasma using competitive immunoassay. The method has a LLOQ of 1.952 pg/mL for estradiol. Values below the LLOQ were set to 0.
Measured: Baseline, and at Cycle 1 Week 4 prior to any study drug (each cycle is defined as 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2017
- Study start15 Sep 2017
- Primary completion25 Apr 2022
- Study completion25 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03312738
- Sponsor's protocol ID
- CRAD001Y2202
- Acronym
- BOLERO-5
- Status last verified
- Apr 2023
- First submitted
- 15 Sep 2017
- Last updated
- 23 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Shao ZM, Cai L, Wang S, Hu X, Shen K, Wang H, Li H, Feng J, Liu Q, Cheng J, Wu X, Wang X, Li H, Luo T, Liu J, Amin K, Slimane K, Qiao Y, Liu Y, Tong Z. BOLERO-5: a phase II study of everolimus and exemestane combination in Chinese post-menopausal women with ER + /HER2- advanced breast cancer. Discov Oncol. 2024 Jun 21;15(1):237. doi: 10.1007/s12672-024-01027-8.
PubMed 38904918
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03312738
- Acronym / sponsor ID
- BOLERO-5 / CRAD001Y2202
- Conditions
- Advanced Breast Cancer
- Keywords
- everolimus, exemestane, advanced Breast Cancer, non-steroidal aromatase inhibitors, breast carcinoma, breast cancer, breast lump, HER2 negative
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 159 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Sep 2017 (actual)
- Primary completion
- 25 Apr 2022 (actual)
- Study completion
- 25 Apr 2022 (actual)
- First posted
- 18 Oct 2017 (actual)
- Results
- Posted 23 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aimed at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer after recurrence or progression on letrozole or anastrozole.
Detailed description
This was a multicenter, double-blind, randomized, placebo-controlled, phase II study evaluating treatment with everolimus (10 mg daily) in combination with exemestane (25 mg daily) vs placebo in combination with exemestane (25 mg daily) in Chinese postmenopausal women with locally advanced, recurrent or metastatic ER+ HER2- breast cancer refractory to non-steroidal aromatase inhibitors.
Randomized participants started the study treatment at Cycle 1 Day 1, and were treated continuously until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from treatment for any other reason.
After end of treatment, all participants were followed up for safety up to 30 days after last dose of study treatment (exemestane and/or everolimus/placebo). All participants were followed for survival status at least every 3 months after treatment discontinuation unless they discontinued due to death, consent withdrawal or lost to follow-up
If a participants permanently discontinued study treatment for reasons other than disease progression, death, lost to follow-up, or withdrawal of consent to efficacy follow-up then they entered the post-treatment efficacy follow-up period until disease progression, death, lost to follow-up or withdrawal of consent for efficacy follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus + Exemestane | Experimental | Drug: Everolimus, Drug: ExemestaneParticipants received everolimus as a continuous oral daily dose of 10 mg and exemestane as a continuous oral daily dose of 25 mg |
| Placebo + Exemestane | Active comparator | Drug: Exemestane, Drug: Everolimus PlaceboParticipants received placebo as a continuous oral daily dose and exemestane as a continuous oral daily dose of 25 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Chinese Postmenopausal women with ER+ HER2- 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 was defined either by:
- Recurrence or progression on prior NSAI was defined as:
- Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment
Key exclusion criteria (6 listed)
- HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test.
- Patients who had received more than one chemotherapy line for ABC
- Patients with symptomatic visceral disease and candidates 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 used at the time of study entry except topical applications, inhaled sprays, eye drops or local injections.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: RAD001Everolimus was formulated as tablets of 5 mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) was administered in a blinded manner by continuous oral daily dosing. | Drug | Everolimus + Exemestane |
| ExemestaneCommercially available exemestane was supplied as 25 mg tablets. Exemestane was administered as continuous oral daily dose of 25 mg tablets. | Drug | Everolimus + Exemestane, Placebo + Exemestane |
| Everolimus PlaceboPlacebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) was administered in a blinded manner by continuous oral daily dosing. | Drug | Placebo + Exemestane |
Primary outcome
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment
Time frame: From randomization up to date of first documented progression or death, assessed up to approximately 3.5 years
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the local investigator's tumor assessment per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
16 secondary outcomes
Progression-free Survival (PFS) Based on Blinded Independent Review Committee (BIRC) Assessment
Time frame: From randomization up to date of first documented progression or death, assessed up to approximately 1.8 years
Overall Survival (OS)
Time frame: From randomization to date of death, up to approximately 3.8 years
Overall Response Rate (ORR) Based on Local Radiology Review of Tumor Assessment
Time frame: Up to approximately 3.5 years
Overall Response Rate (ORR) Based on BIRC Assessment
Time frame: Up to approximately 1.8 years
Clinical Benefit Rate (CBR) Based on Local Radiology Review of Tumor Assessment
Time frame: Up to approximately 3.5 years
Clinical Benefit Rate (CBR) Based on BIRC Assessment
Time frame: Up to approximately 1.8 years
Time to Response (TTR) Based on Local Radiology Review of Tumor Assessment
Time frame: Up to approximately 3.5 years
Time to Response (TTR) Based on BIRC Assessment
Time frame: Up to approximately 1.8 years
Duration of Response (DOR) Based on Local Radiology Review of Tumor Assessment
Time frame: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 3.5 years
Duration of Response (DOR) Based on BIRC Assessment
Time frame: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 1.8 years
Time to Definitive Deterioration of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score From Baseline
Time frame: From randomization up to definitive deterioration of the ECOG PS by one categotu of the score, assessed up to approximately 3.5 years
Everolimus Predose Concentration (Cmin)
Time frame: Predose on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Everolimus Concentration at 2 Hours Post Dose (C2h)
Time frame: Two hours post everolimus administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Exemestane Predose Concentration (Cmin)
Time frame: Predose of exemestane on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Exemestane Concentration at 2 Hours Post Dose (C2h)
Time frame: Two hours post exemestane administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Estradiol Levels After 4 Weeks of Study Treatment
Time frame: Baseline, and at Cycle 1 Week 4 prior to any study drug (each cycle is defined as 4 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38904918Shao ZM, Cai L, Wang S, Hu X, Shen K, Wang H, Li H, Feng J, Liu Q, Cheng J, Wu X, Wang X, Li H, Luo T, Liu J, Amin K, Slimane K, Qiao Y, Liu Y, Tong Z. BOLERO-5: a phase II study of everolimus and exemestane combination in Chinese post-menopausal women with ER + /HER2- advanced breast cancer. Discov Oncol. 2024 Jun 21;15(1):237. doi: 10.1007/s12672-024-01027-8.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and Exemestane in people with Advanced Breast Cancer, run by Novartis Pharmaceuticals at 15 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment (time frame: From randomization up to date of first documented progression or death, assessed up to approximately 3.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03312738, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.