Metastatic Breast CancerPhase 3MACS2096NCT01626222
4EVER - Efficacy, Safety, Health Economics, Translational Research of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer
A Phase 3 study testing Exemestane and Everolimus (RAD001) in people with Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 84 sites in Germany.
Trial summary
The present multi-center, open-label, single-arm study aims to evaluate the efficacy and safety, quality of life and health resources utilization in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with non-steroidal aromatase inhibitors (NSAI) treated with the… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Exemestane and Everolimus (RAD001)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 301 participants
- Where
- 84 sitesGermany
- Study dates
- Jun 2012to Nov 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
Main Inclusion criteria:
Metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy or any other non-systemic treatment.
Histological or cytological confirmation of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer Postmenopausal women. Disease progression following prior therapy with non steroidal aromatase inhibitors (NSAI), defined as: Recurrence while on, or following completion of an adjuvant treatment with Letrozole or Anastrozole, or Progression while on or following completion of Letrozole or Anastrozole treatment for ABC/MBC.
Radiological evidence of recurrence or progression on last systemic therapy prior to enrollment.
Patients must have at least one lesion that can be accurately measured or bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease.
Written informed consent obtained before any screening procedure and according to local guidelines.
Other protocol defined inclusion criteria apply.
Main Exclusion criteria:
HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
Previous treatment with mTOR inhibitors or known hypersensitivity to mTOR inhibitors.
Symptomatic brain or other CNS metastases. Previously treated brain metastases are allowed provided the patient is free of symptoms, prior radiotherapy for brain metastasis was more than four weeks before enrollment and the dose of corticosteroids is low (i.e. ≤ 10 mg/d Prednisolone equivalent) and stable for at least two weeks prior to enrollment.
Patients with Hepatitis B or C or with a history of Hepatitis B or C. Patients unwilling to or unable to comply with the protocol. Other protocol defined exclusion criteria apply.
Trial locations and contacts
84 sites in 1 country.
84 sites in 1 country
Germany84 sites
Novartis Investigative Site
Aachen, 52074
Novartis Investigative Site
Amberg, 92224
Novartis Investigative Site
Augsburg, 86150
Novartis Investigative Site
Augsburg, 86156
Novartis Investigative Site
Bergisch Gladbach, 51465
Novartis Investigative Site
Berlin, Germany, 12203
Novartis Investigative Site
Berlin, 10367
Novartis Investigative Site
Berlin, 10707
Novartis Investigative Site
Berlin, 12552
Novartis Investigative Site
Berlin, 12683
Novartis Investigative Site
Berlin, 14169
Novartis Investigative Site
Berlin, 14195
Novartis Investigative Site
Böblingen, 71032
Novartis Investigative Site
Bochum, 44787
Novartis Investigative Site
Bonn, 53105
Novartis Investigative Site
Bonn, 53111
Novartis Investigative Site
Bottrop, 46236
Novartis Investigative Site
Braunschweig, 38100
Novartis Investigative Site
Bremen, 28209
Novartis Investigative Site
Chemnitz, 09113
Novartis Investigative Site
Cologne, 50935
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Donauwörth, 86609
Novartis Investigative Site
Dresden, 01127
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Essen, 45136
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Esslingen am Neckar, 73730
Novartis Investigative Site
Eutin, 23701
Novartis Investigative Site
Frankfurt, 60389
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Fulda, 36043
Novartis Investigative Site
Fürstenwalde, 15517
Novartis Investigative Site
Fürth, 90766
Novartis Investigative Site
Gera, 07548
Novartis Investigative Site
Gerlingen, 70839
Novartis Investigative Site
Goslar, 38642
Novartis Investigative Site
Gütersloh, 33332
Novartis Investigative Site
Halle, 06110
Novartis Investigative Site
Halle, 06120
Novartis Investigative Site
Hamburg, 20249
Novartis Investigative Site
Hanover, 30177
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Kassel, 34125
Novartis Investigative Site
Kiel, 24103
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Langen, 63225
Novartis Investigative Site
Lemgo, 32657
Novartis Investigative Site
Lüneburg, 21339
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Mannheim, 68165
Novartis Investigative Site
Marburg, 35039
Novartis Investigative Site
Memmingen, 87700
Novartis Investigative Site
Mönchengladbach, 41061
Novartis Investigative Site
Mühlhausen, 99974
Novartis Investigative Site
Mülheim, 45468
Novartis Investigative Site
München, 80637
Novartis Investigative Site
München, 80638
Novartis Investigative Site
München, 81241
Novartis Investigative Site
München, 81377
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Nuremberg, 90403
Novartis Investigative Site
Oldenburg, 26121
Novartis Investigative Site
Plauen-Kauschwitz, 08525
Novartis Investigative Site
Ravensburg, 88214
Novartis Investigative Site
Recklinghausen, 45657
Novartis Investigative Site
Rosenheim, 83022
Novartis Investigative Site
Rostock, 18057
Novartis Investigative Site
Singen, 78224
Novartis Investigative Site
Soest, 59494
Novartis Investigative Site
Speyer, 67346
Novartis Investigative Site
Stralsund, 18435
Novartis Investigative Site
Stuttgart, 70178
Novartis Investigative Site
Trier, 54290
Novartis Investigative Site
Troisdorf, 53840
Novartis Investigative Site
Tübingen, 72076
Novartis Investigative Site
Velbert, 42551
Novartis Investigative Site
Villingen-Schwenningen, 78052
Novartis Investigative Site
Weißenfels, 06667
Novartis Investigative Site
Wuppertal, 42105
About this study
Official title: A Phase IIIB, Multi-Center, Open Label Study For Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) in Combination With Exemestane: 4EVER - Efficacy, Safety, Health Economics, Translational Research
The present multi-center, open-label, single-arm study aims to evaluate the efficacy and safety, quality of life and health resources utilization in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with non-steroidal aromatase inhibitors (NSAI) treated with the combination of Everolimus and Exemestane.
Read the detailed description
In light of the need for new treatment options for postmenopausal, hormone receptor positive, HER2 negative women after failure of prior non-steroidal aromatase inhibitor (NSAI) therapy, the BOLERO-2 trial was performed and demonstrated significant efficacy of the combinatorial treatment of Everolimus and Exemestane compared to an Exemestane monotherapy in this setting.
In this randomized, double blind, placebo-controlled trial a statistically significant improvement in progression-free survival (PFS) by adding Everolimus to exemestane versus Exemestane alone was reported. Adding Everolimus determined a 2.4-fold prolongation in PFS from 3.2 up to 7.4 months and so lowered the risk of cancer progression by 56% for these women. These findings were confirmed by an independent assessment (4.1 vs. 11.0 months, risk reduction: 64%). The quality of life data shows positive trend in the Everolimus plus Exemestane treatment arm. (Baselga 2011, Hortobagyi 2011). Thus, the benefit of the combinatorial treatment versus Exemestane monotherapy was shown in a defined patient population under controlled conditions.
The primary objective of this trial to assess the Overall Response Rate (ORR) in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with NSAIs treated with the combination of Everolimus and Exemestane. The secondary objectives include, Progression free survival (PFS), Overall survival (OS), Safety, Change in Quality of life scores over time, Health resource utilization. The exploratory objectives reflect scientific interest within the treatment of metastatic breast cancer and are to be modified, if applicable, according to the current scientific state of the art at the time of actual analysis. These include: the influence of age, performance status, cancer activity and inflammation on anxiety and depression; changes in serum bone-turnover biomarkers; Pharmacogenetics of Everolimus in patients with advanced breast cancer; presence and molecular characteristics of Circulating Tumor Cells; correlation of response to Exemestane/Everolimus with Proteomic analysis.
The present national, multi-center, open-label, single-arm study aims to evaluate the efficacy and safety, quality of life and health resources utilization of the combination of Everolimus and Exemestane in a broader patient population compared to BOLERO-2, i.e. without limitations as to the number of previous chemotherapy lines, the time point of progression after NSAI therapy, and the previous endocrine therapy as patients under Exemestane monotherapy may be enrolled. Since the combination was shown to significantly improve PFS in the previous BOLERO-2 trial, for ethical reasons no endocrine comparator drugs will be investigated in the present study, due to the low efficacy of Exemestane monotherapy (PFS 3.2 months).
- Conditions
- Metastatic Breast Cancer
- Being tested
- Exemestane, Everolimus (RAD001)
- Keywords
- Postmenopausal, Estrogen Receptor Positive, HER2 negative, Locally Advanced, Metastatic Breast Cancer, Everolimus (RAD001), Exemestane
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExemestaneDrug
Exemestane is supplied by Novartis until Everolimus is commercially available for the study setting. Afterwards the investigator will prescribe Exemestane according to the individual label. Commercially available Exemestane will be supplied as tablets of 25 mg strength for oral administration. Complete guidelines for management and administration of Exemestane can be found in the package insert. Exemestane will be dosed starting on treatment Day 1. Patients will be instructed to take 1 tablet of 25 mg Exemestane orally. Package insert instructions should be followed. On the first day of each cycle, patients will receive an adequate drug supply (before commercial availability) or a prescription (after commercial availability) for self-administration at home. The investigator must emphasize compliance and will instruct the patient to take Exemestane exactly as prescribed.
Everolimus (RAD001)Drug
Everolimus (RAD001) is supplied by Novartis until Everolimus is commercially available for the study setting. Afterwards the investigator will prescribe Everolimus according to the individual label. Everolimus is formulated as tablets of 10 and 5 mg strength for oral administration. All study medication will be packaged into blister packs. The blisters should be opened only at the time of administration, as the drugs are both hygroscopic and light sensitive. Everolimus will be dosed starting on treatment Day 1. Patients will be instructed to take 1 tablet × 10 mg Everolimus orally with a large glass of water once daily at the same time each day with or without food. On the first day of each cycle, patients will receive an adequate drug supply (before commercial availability) or a prescription (after commercial availability) for self-administration at home. The investigator must emphasize compliance and will instruct the patient to take Everolimus exactly as prescribed.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus & Exemestane | Experimental | This study will be performed in 300 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer progressing following prior therapy with non-steroidal aromatase inhibitors (NSAI) as defined by: 1. Recurrence while on or after completion of an adjuvant treatment including Letrozole or Anastrozole, or 2. Progression while on or following the completion of Letrozole or Anastrozole treatment for locally advanced or metastatic breast cancer. Except for prior use of mTOR inhibitors, there are no restrictions as to the last anticancer treatment prior to enrollment. Patients must have documented evidence of recurrence or progression on last therapy prior to enrollment. Written informed consent must be obtained prior to any screening procedures. The investigator or designee must ensure that only patients who meet all the following inclusion and none of the exclusion criteria are offered enrollment in the study. Receives: Drug: Exemestane; Drug: Everolimus (RAD001) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) after 24 weeks of treatment
The Overall response rate (ORR) is the proportion of patients with a best overall response of confirmed complete (CR) or partial (PR) response by Week 24. The best overall response is determined from the sequence of investigator overall lesion responses according to RECIST 1.1. 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.
Measured: 24 weeks
Secondary outcomes (6)
Progression free survival (PFS) after 48 weeks of treatment
Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Measured: 48 weeks
Overall Response Rate (ORR) after 48 weeks of treatment
The ORR by Week 48 will be derived from the sequence of overall lesion responses as described for the primary efficacy variable. The ORR by Week 48 will be summarized using frequency tables presenting absolute and relative frequencies together with appropriate confidence intervals
Measured: 48 weeks
Overall survival (OS) after 48 weeks of treatment
Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact. OS will be summarized using the Kaplan-Meier method.
Measured: 48 weeks
Safety within 48 weeks of treatment
The assessment of safety will be based mainly on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g. vital signs, and special tests) will be considered as appropriate. For all safety analyses, the safety set will be used.
Measured: 48 weeks
Resource utilization
Data relating to Resource Utilization will be used for the purpose of economic evaluation, which will be carried out and reported as a separate activity.
The study population receiving RAD001 plus Exemestane will be compared to alternative cohorts (e.g., purely endocrine treatment with Fulvestrant monotherapy, Exemestane monotherapy or chemotherapy, e.g. Capecitabine) using a Markov model. For each alternative therapy option, median PFS, OS and health-related quality of life will be determined by a systematic review of literature or databases.
Measured: 48 weeks
Health-related quality of life
Health-related quality of life (HRQoL) will be assessed using the EORTC QLQ-C30 and BR23 questionnaires and the EuroQoL EQ-5D questionnaire. The HADS D questionnaire will be used to assess anxiety and depression. Scoring will follow the instructions of the respective manuals.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2012 (estimated)
- Study startJun 2012
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic 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
- 301 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
- NCT01626222
- Sponsor's protocol ID
- CRAD001JDE49
- Acronym
- MACS2096
- Status last verified
- Feb 2017
- First submitted
- 20 Jun 2012
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Hadji P, Stoetzer O, Decker T, Kurbacher CM, Marme F, Schneeweiss A, Mundhenke C, Distelrath A, Fasching PA, Lux MP, Luftner D, Janni W, Muth M, Kreuzeder J, Quiering C, Grischke EM, Tesch H. The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial. J Bone Oncol. 2018 Oct 2;14:010-10. doi: 10.1016/j.jbo.2018.09.010. eCollection 2019 Feb.
PubMed 30515367Tesch H, Stoetzer O, Decker T, Kurbacher CM, Marme F, Schneeweiss A, Mundhenke C, Distelrath A, Fasching PA, Lux MP, Luftner D, Hadji P, Janni W, Muth M, Kreuzeder J, Quiering C, Taran FA. Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial. Int J Cancer. 2019 Feb 15;144(4):877-885. doi: 10.1002/ijc.31738. Epub 2018 Oct 30.
PubMed 29992557
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIB, Multi-Center, Open Label Study For Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) in Combination With Exemestane: 4EVER - Efficacy, Safety, Health Economics, Translational Research
- ClinicalTrials.gov ID
- NCT01626222
- Acronym / sponsor ID
- MACS2096 / CRAD001JDE49
- Conditions
- Metastatic Breast Cancer
- Keywords
- Postmenopausal, Estrogen Receptor Positive, HER2 negative, Locally Advanced, Metastatic Breast Cancer, Everolimus (RAD001), Exemestane
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 301 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 22 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present multi-center, open-label, single-arm study aims to evaluate the efficacy and safety, quality of life and health resources utilization in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with non-steroidal aromatase inhibitors (NSAI) treated with the combination of Everolimus and Exemestane.
Detailed description
In light of the need for new treatment options for postmenopausal, hormone receptor positive, HER2 negative women after failure of prior non-steroidal aromatase inhibitor (NSAI) therapy, the BOLERO-2 trial was performed and demonstrated significant efficacy of the combinatorial treatment of Everolimus and Exemestane compared to an Exemestane monotherapy in this setting.
In this randomized, double blind, placebo-controlled trial a statistically significant improvement in progression-free survival (PFS) by adding Everolimus to exemestane versus Exemestane alone was reported. Adding Everolimus determined a 2.4-fold prolongation in PFS from 3.2 up to 7.4 months and so lowered the risk of cancer progression by 56% for these women. These findings were confirmed by an independent assessment (4.1 vs. 11.0 months, risk reduction: 64%). The quality of life data shows positive trend in the Everolimus plus Exemestane treatment arm. (Baselga 2011, Hortobagyi 2011). Thus, the benefit of the combinatorial treatment versus Exemestane monotherapy was shown in a defined patient population under controlled conditions.
The primary objective of this trial to assess the Overall Response Rate (ORR) in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with NSAIs treated with the combination of Everolimus and Exemestane. The secondary objectives include, Progression free survival (PFS), Overall survival (OS), Safety, Change in Quality of life scores over time, Health resource utilization. The exploratory objectives reflect scientific interest within the treatment of metastatic breast cancer and are to be modified, if applicable, according to the current scientific state of the art at the time of actual analysis. These include: the influence of age, performance status, cancer activity and inflammation on anxiety and depression; changes in serum bone-turnover biomarkers; Pharmacogenetics of Everolimus in patients with advanced breast cancer; presence and molecular characteristics of Circulating Tumor Cells; correlation of response to Exemestane/Everolimus with Proteomic analysis.
The present national, multi-center, open-label, single-arm study aims to evaluate the efficacy and safety, quality of life and health resources utilization of the combination of Everolimus and Exemestane in a broader patient population compared to BOLERO-2, i.e. without limitations as to the number of previous chemotherapy lines, the time point of progression after NSAI therapy, and the previous endocrine therapy as patients under Exemestane monotherapy may be enrolled. Since the combination was shown to significantly improve PFS in the previous BOLERO-2 trial, for ethical reasons no endocrine comparator drugs will be investigated in the present study, due to the low efficacy of Exemestane monotherapy (PFS 3.2 months).
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: Exemestane, Drug: Everolimus (RAD001)This study will be performed in 300 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer progressing following prior therapy with non-steroidal aromatase inhibitors (NSAI) as defined by: 1. Recurrence while on or after completion of an adjuvant treatment including Letrozole or Anastrozole, or 2. Progression while on or following the completion of Letrozole or Anastrozole treatment for locally advanced or metastatic breast cancer. Except for prior use of mTOR inhibitors, there are no restrictions as to the last anticancer treatment prior to enrollment. Patients must have documented evidence of recurrence or progression on last therapy prior to enrollment. Written informed consent must be obtained prior to any screening procedures. The investigator or designee must ensure that only patients who meet all the following inclusion and none of the exclusion criteria are offered enrollment in the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| ExemestaneExemestane is supplied by Novartis until Everolimus is commercially available for the study setting. Afterwards the investigator will prescribe Exemestane according to the individual label. Commercially available Exemestane will be supplied as tablets of 25 mg strength for oral administration. Complete guidelines for management and administration of Exemestane can be found in the package insert. Exemestane will be dosed starting on treatment Day 1. Patients will be instructed to take 1 tablet of 25 mg Exemestane orally. Package insert instructions should be followed. On the first day of each cycle, patients will receive an adequate drug supply (before commercial availability) or a prescription (after commercial availability) for self-administration at home. The investigator must emphasize compliance and will instruct the patient to take Exemestane exactly as prescribed. | Drug | Everolimus & Exemestane |
| Everolimus (RAD001)Everolimus (RAD001) is supplied by Novartis until Everolimus is commercially available for the study setting. Afterwards the investigator will prescribe Everolimus according to the individual label. Everolimus is formulated as tablets of 10 and 5 mg strength for oral administration. All study medication will be packaged into blister packs. The blisters should be opened only at the time of administration, as the drugs are both hygroscopic and light sensitive. Everolimus will be dosed starting on treatment Day 1. Patients will be instructed to take 1 tablet × 10 mg Everolimus orally with a large glass of water once daily at the same time each day with or without food. On the first day of each cycle, patients will receive an adequate drug supply (before commercial availability) or a prescription (after commercial availability) for self-administration at home. The investigator must emphasize compliance and will instruct the patient to take Everolimus exactly as prescribed. | Drug | Everolimus & Exemestane |
Primary outcome
Overall Response Rate (ORR) after 24 weeks of treatment
Time frame: 24 weeks
The Overall response rate (ORR) is the proportion of patients with a best overall response of confirmed complete (CR) or partial (PR) response by Week 24. The best overall response is determined from the sequence of investigator overall lesion responses according to RECIST 1.1. 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.
6 secondary outcomes
Progression free survival (PFS) after 48 weeks of treatment
Time frame: 48 weeks
Overall Response Rate (ORR) after 48 weeks of treatment
Time frame: 48 weeks
Overall survival (OS) after 48 weeks of treatment
Time frame: 48 weeks
Safety within 48 weeks of treatment
Time frame: 48 weeks
Resource utilization
Time frame: 48 weeks
Health-related quality of life
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
- Derived from this study: PubMed 30515367Hadji P, Stoetzer O, Decker T, Kurbacher CM, Marme F, Schneeweiss A, Mundhenke C, Distelrath A, Fasching PA, Lux MP, Luftner D, Janni W, Muth M, Kreuzeder J, Quiering C, Grischke EM, Tesch H. The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial. J Bone Oncol. 2018 Oct 2;14:010-10. doi: 10.1016/j.jbo.2018.09.010. eCollection 2019 Feb.
- Derived from this study: PubMed 29992557Tesch H, Stoetzer O, Decker T, Kurbacher CM, Marme F, Schneeweiss A, Mundhenke C, Distelrath A, Fasching PA, Lux MP, Luftner D, Hadji P, Janni W, Muth M, Kreuzeder J, Quiering C, Taran FA. Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial. Int J Cancer. 2019 Feb 15;144(4):877-885. doi: 10.1002/ijc.31738. Epub 2018 Oct 30.
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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
84 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Exemestane and Everolimus (RAD001) in people with Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 84 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 84 sites in Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall Response Rate (ORR) after 24 weeks of treatment (time frame: 24 weeks). 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 NCT01626222, which also lists 2 linked publications.
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 Feb 2017.