Post Menopausal Breast CancerPhase 3EVEREXESNCT03176238
Study in Post-menopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer
A Phase 3 study testing everolimus and exemestane in people with Post Menopausal Breast Cancer, run by Novartis Pharmaceuticals at 55 sites in 13 countries.
Trial summary
This international, multi-center, open-label, single-arm study evaluated the safety and tolerability profile of everolimus in post-menopausal women with HR positive, HER2 negative locally advanced or metastatic breast cancer after documented recurrence or progression following a non-steroidal aromatase inhibitors… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Post Menopausal Breast Cancer
- What is being tested?
- everolimus and exemestane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 235 participants
- Where
- 55 sitesin 13 countries
- Study dates
- 29 Mar 2013to 29 Jan 2019
- Phase
- Phase 3
- 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
- Postmenopausal women with metastatic, recurrent or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
- Histological or cytological confirmation of hormone-receptor positive (HR+) breast cancer.
- Disease refractory to non-steroidal aromatase inhibitors, defined as:
- Recurrence while on, or within 12 months (365 days) of completion of adjuvant therapy with letrozole or anastrozole, or
- Progression while on, or within one month (30 days) of completion of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer (ABC).
- Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.
Show all 12Show fewer
- Patients must have had:
- At least one lesion that could have been accurately measured in at least one dimension
- 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI, or
- Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above.
- Adequate bone marrow, coagulation, liver and renal function.
- ECOG performance status ≤ 2.
Who cannot join
- Patients overexpressing HER2 by local laboratory testing (IHC 3+ staining or in situ hybridization positive). Patients with IHC 2+ must have a negative in situ hybridization test.
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
- Patients with more than one prior chemotherapy line for ABC. A chemotherapy line is an anticancer regimen(s) that contained at least 1 cytotoxic chemotherapy agent, given for a minimum of 21 days.
- Previous treatment with mTOR inhibitors.
- Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
- Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline was not required.
- Patient who were being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A
- History of brain or other CNS metastases, including leptomeningeal metastasis.
Trial locations and contacts
55 sites in 13 countries.
55 sites in 13 countries
South Korea13 sites
Novartis Investigative Site
Busan, 602739
Novartis Investigative Site
Gyeonggi-do, Korea, 10408
Novartis Investigative Site
Jeollanam-do, Jeollanam-do, 519763
Novartis Investigative Site
Seoul, Korea, 05505
Novartis Investigative Site
Seoul, Seocho Gu, 06591
Novartis Investigative Site
Seoul, 01812
Novartis Investigative Site
Seoul, 02841
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 06273
Novartis Investigative Site
Seoul, 06351
Novartis Investigative Site
Suwon, Gyeonggi-do, 443380
Novartis Investigative Site
Taegu, 41944
Australia7 sites
Novartis Investigative Site
Box Hill, Victoria, 3128
Novartis Investigative Site
Caringbah, New South Wales, 2229
Novartis Investigative Site
Garran, Australian Capital Territory, 2605
Novartis Investigative Site
Heidelberg, Victoria, 3084
Novartis Investigative Site
Liverpool, New South Wales, 2170
Novartis Investigative Site
Ringwood East, Victoria, 3135
Novartis Investigative Site
St Albans, Victoria, 3021
Turkey (Türkiye)7 sites
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Ankara, 06460
Novartis Investigative Site
Ankara, 06500
Novartis Investigative Site
Gaziantep, 27310
Novartis Investigative Site
Izmir, 35040
Novartis Investigative Site
Kartal, 34890
Novartis Investigative Site
Pendik / Istanbul, Turkey, 34899
Taiwan6 sites
Novartis Investigative Site
Changhua, 50006
Novartis Investigative Site
Kaohsiung City, 83301
Novartis Investigative Site
Kaoshiung, Taiwan, 80756
Novartis Investigative Site
New Taipei City, TWN, 23561
Novartis Investigative Site
Taipei, 10048
Novartis Investigative Site
Taipei, 10449
India4 sites
Novartis Investigative Site
Cuttack, Odisha, 753 007
Novartis Investigative Site
Karamsad, Gujarat, 388325
Novartis Investigative Site
Nashik, Maharashtra, 422 004
Novartis Investigative Site
Pune, Maharashtra, 411013
Indonesia4 sites
Novartis Investigative Site
Bandung, 40161
Novartis Investigative Site
Jakarta, 11420
Novartis Investigative Site
Semarang, 50212
Novartis Investigative Site
Yogyakarta, 55284
Malaysia3 sites
Novartis Investigative Site
Kota Kinabalu, Sabah, 88586
Novartis Investigative Site
Kuala Lumpur, Kuala Lumpur, 50586
Novartis Investigative Site
Kuala Lumpur, MYS, 56000
South Africa3 sites
Novartis Investigative Site
Cape Town, Western Cape, 7925
Novartis Investigative Site
George, Western Cape, 6530
Novartis Investigative Site
Western Cape, Western Cape, 7925
Thailand3 sites
Novartis Investigative Site
Bangkok, 10300
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Chiang Mai, 50200
Morocco2 sites
Novartis Investigative Site
Casablanca
Novartis Investigative Site
Rabat, 6527
About this study
Official title: A Phase IIIb, Multi-center, Open-label Study of RAD001 in Combination With EXemestane in Post-menopausal Women With EStrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Locally Advanced or Metastatic Breast Cancer
This international, multi-center, open-label, single-arm study evaluated the safety and tolerability profile of everolimus in post-menopausal women with HR positive, HER2 negative locally advanced or metastatic breast cancer after documented recurrence or progression following a non-steroidal aromatase inhibitors (NSAI) therapy in Novartis Oncology emergent growth market (EGM) countries.Data was presented by Asian countries vs Non-Asian countries to confirm no difference in safety and efficacy. Summary statistics were presented.
- Conditions
- Post Menopausal Breast Cancer
- Being tested
- everolimus, exemestane
- Keywords
- post menopausal, advanced breast cancer, metastatic breast cancer, everolimus, exemestane, mTor inhibitor, endocrine therapy, human epidermal growth factor, estrogen receptor positive, adult, CRAD001
- 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
one 10 mg tablet or two 5 mg tablets of everolimus were administered orally once daily on a continuous dosing schedule starting on Day 1
exemestaneDrug
25 mg tablet was administered orally once daily on a continuous dosing schedule starting on Day 1
| Study group | Role | What they receive |
|---|---|---|
| everolimus + exemestane | Experimental | Everolimus (10 mg) and exemestane (25 mg) tablets taken orally in combination once daily Receives: Drug: everolimus; Drug: exemestane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of Number of Participants With Treatment Emergent Adverse Events (TEAE) - All Grades
Adverse events (AEs), serious adverse events (SAEs), changes from baseline in vital signs and laboratory results (hematology, blood chemistry, lipid profile) qualifying and reported as AEs. Although a patient might had two or more adverse events the patient is only counted once in a category. The same patient might appear in different categories. AESI: Adverse events of special interest.
Measured: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries including a 30 day post treatment follow up period
Secondary outcomes (4)
Percentage of Participants Response Rates (Best Overall and Overall)
The best overall response for each patient is determined from the sequence of investigator overall lesion responses according to RECIST 1.1: Complete Response (CR)=disappearance of target lesions, Partial Response (PR) was >=30% decrease in sum of diameter of lesions, Progressive Disease (PD) was >=20% decrease in sum of diameter of lesions, Stable Disease (SD) does not qualify for PR, CR or PD, Unknown=not documented or assessed. To be assigned a best overall response of CR at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best overall response of PR at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required. The Overall response rate (ORR) is the percentage of patients with a best overall response of confirmed complete (CR) or partial (PR) response. The 95% confidence intervals (CI) were computed using the Clopper-Pearson method
Measured: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
Percentage of Participants Clinical Benefit Rate
Clinical benefit rate: Patients with best overall response rate of CR (any duration), PR (any duration) and SD with duration of 24 weeks or longer according to RECIST 1.1 criteria: Complete Response (CR)=disappearance of target lesions, Partial Response (PR) was >=30% decrease in sum of diameter of lesions, Progressive Disease (PD) was >=20% decrease in sum of diameter of lesions, Stable Disease (SD) does not qualify for PR, CR or PD, Unknown=not documented or assessed. Best overall response of CR = at least two determinations of CR at least 4 weeks apart before progression are required. Best overall response of PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required. The Overall response rate (ORR) is the percentage of patients with a best overall response of confirmed complete (CR) or partial (PR) response. The 95% confidence intervals (CI) were computed using the Clopper-Pearson method.
Measured: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
Progression Free Survival (PFS)
PFS is time from date of start of treatment to date of disease progression or death due to any cause, whichever occurs first.
b Percentiles with 95% CIs are calculated from PROC LIFETEST output using method of Brookmeyer and Crowley (1982)
Measured: Baseline up to approximately 43 weeks for Asian countires and 40 weeks for Non-Asian countries
Percent of Participants Event-free Probability Estimates of Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status
Time to deterioration of ECOG performance status, from baseline will be assessed using the ECOG Performance Status Scale (Oken, 1982). Time to deterioration is the time from date of start of treatment to the date of the event defined as deterioration. Deterioration is defined as an increase in performance status from 0 to 2 or greater, an increase in performance status from 1-2 to 3 or greater, or death due to any cause. Event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point. Event-free probability estimates were are obtained from the Kaplan-Meier survival estimates.
Measured: Baseline up to approximately 50 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2017
- Study start29 Mar 2013
- Primary completion29 Jan 2019
- Study completion29 Jan 2019
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.
- Other trials for Post Menopausal 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 235 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
- NCT03176238
- Sponsor's protocol ID
- CRAD001JIC06
- Acronym
- EVEREXES
- Status last verified
- Apr 2020
- First submitted
- 1 Jun 2017
- Last updated
- 7 Apr 2020
- 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIb, Multi-center, Open-label Study of RAD001 in Combination With EXemestane in Post-menopausal Women With EStrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Locally Advanced or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT03176238
- Acronym / sponsor ID
- EVEREXES / CRAD001JIC06
- Conditions
- Post Menopausal Breast Cancer
- Keywords
- post menopausal, advanced breast cancer, metastatic breast cancer, everolimus, exemestane, mTor inhibitor, endocrine therapy, human epidermal growth factor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 235 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2013 (actual)
- Primary completion
- 29 Jan 2019 (actual)
- Study completion
- 29 Jan 2019 (actual)
- First posted
- 5 Jun 2017 (actual)
- Results
- Posted 7 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This international, multi-center, open-label, single-arm study evaluated the safety and tolerability profile of everolimus in post-menopausal women with HR positive, HER2 negative locally advanced or metastatic breast cancer after documented recurrence or progression following a non-steroidal aromatase inhibitors (NSAI) therapy in Novartis Oncology emergent growth market (EGM) countries.Data was presented by Asian countries vs Non-Asian countries to confirm no difference in safety and efficacy. Summary statistics were presented.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| everolimus + exemestane | Experimental | Drug: everolimus, Drug: exemestaneEverolimus (10 mg) and exemestane (25 mg) tablets taken orally in combination once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Postmenopausal women with metastatic, recurrent or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
- Histological or cytological confirmation of hormone-receptor positive (HR+) breast cancer.
- Disease refractory to non-steroidal aromatase inhibitors, defined as:
- Recurrence while on, or within 12 months (365 days) of completion of adjuvant therapy with letrozole or anastrozole, or
- Progression while on, or within one month (30 days) of completion of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer (ABC).
Key exclusion criteria (8 listed)
- Patients overexpressing HER2 by local laboratory testing (IHC 3+ staining or in situ hybridization positive). Patients with IHC 2+ must have a negative in situ hybridization test.
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
- Patients with more than one prior chemotherapy line for ABC. A chemotherapy line is an anticancer regimen(s) that contained at least 1 cytotoxic chemotherapy agent, given for a minimum of 21 days.
- Previous treatment with mTOR inhibitors.
- Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
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: RAD001one 10 mg tablet or two 5 mg tablets of everolimus were administered orally once daily on a continuous dosing schedule starting on Day 1 | Drug | everolimus + exemestane |
| exemestane25 mg tablet was administered orally once daily on a continuous dosing schedule starting on Day 1 | Drug | everolimus + exemestane |
Primary outcome
Summary of Number of Participants With Treatment Emergent Adverse Events (TEAE) - All Grades
Time frame: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries including a 30 day post treatment follow up period
Adverse events (AEs), serious adverse events (SAEs), changes from baseline in vital signs and laboratory results (hematology, blood chemistry, lipid profile) qualifying and reported as AEs. Although a patient might had two or more adverse events the patient is only counted once in a category. The same patient might appear in different categories. AESI: Adverse events of special interest.
4 secondary outcomes
Percentage of Participants Response Rates (Best Overall and Overall)
Time frame: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
Percentage of Participants Clinical Benefit Rate
Time frame: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
Progression Free Survival (PFS)
Time frame: Baseline up to approximately 43 weeks for Asian countires and 40 weeks for Non-Asian countries
Percent of Participants Event-free Probability Estimates of Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status
Time frame: Baseline up to approximately 50 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
55 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing everolimus and exemestane in people with Post Menopausal Breast Cancer, run by Novartis Pharmaceuticals at 55 sites in 13 countries.
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 12 inclusion and 8 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 7 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in South Korea, Australia, Turkey (Türkiye), Taiwan, India and 8 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 7 Apr 2020). 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?
Summary of Number of Participants With Treatment Emergent Adverse Events (TEAE) - All Grades (time frame: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries including a 30 day post treatment follow up period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Apr 2020.