Metastatic Breast CancerPhase 3EvelynNCT01773460
Everolimus Beyond Progress for Patients Who Had Progress Under Everolimus and Exemestane
A Phase 3 study testing Everolimus in people with Metastatic Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
Everolimus will be given to patients with metastatic breast cancer who already has a progress taking Everolimus but with a change in the endocrine treatment. 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?
- Everolimus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2013to Jul 2014
- 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
Who may be able to join
- 1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- 2. Complete baseline documentation must be submitted via the web-based data collection system MedCODES® to the GBG Forschungs GmbH.
- 3. Histological confirmed hormone receptor positive (HR+); HER2-negative carcinoma of the breast. Every effort should be made to make paraffin embedded tissue or slides from the original tumor and/or from metastatic tissue available for confirmation of diagnosis and additional translational research.
- 4. Postmenopausal women 5. HER2-negative, hormone-receptor-positive, locally advanced or metastatic stage of disease not amenable to curative treatment by surgery or radiotherapy alone.
- 6. No indication for chemotherapy 7. Patients must have either measurable or non-measurable target lesions according to RECIST criteria. Complete staging work-up within 4 weeks prior to registration including chest and abdominal CT scan or MRI (exceptionally chest X-ray and abdominal ultrasound), and bone scan. Further tests have to be performed according to RECIST or as clinically indicated.
- 8. Disease progression during or after previous exemestane and everolimus treatment as follows (everolimus has to be given previously for at least 12 weeks, treatment-free interval of everolimus for a maximum of 6 weeks until randomization) 9. The following previous systemic treatments are eligible:
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- Previous participation in other everolimus-containing trials, e.g. the GeparQuinto, BOLERO, 4EVER study is allowed.
- (Neo)Adjuvant and up to 1 chemotherapy regimen for metastatic breast cancer
- Maximum of two lines as palliative endocrine monotherapy
- Treatment with bisphosphonates and/or denosumab (adjuvant and/or palliative) 10. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation field or there must be pathologic proof of newly progressive disease.
- 11. Age ≥ 18 years 12. ECOG performance status 0-2 13. Laboratory requirements:
- Absolute neutrophil count at least 1500 cells/microliter,
- hemoglobin ≥9.0 g/dL (hemoglobin <9.0 g/dL is acceptable if it is corrected by growth factor or transfusion)
- platelet count at least 100,000 cells/microliter.
- bilirubin at least 1.5x the upper limit of normal for the institution (ULN);
- elevation of transaminases and alkaline phosphatase <3x ULN or <5x ULN for patients with liver metastases.
- BUN (blood urea nitrogen) ≤ULN
- Fasting plasma glucose (FPG) ≤160 mg/dL or ≤8.9 mmol/L
- Fasting serum cholesterol ≤ 300mg/dl or 7.75mmol/L (LDL cholesterol <190mg/dl) and fasting triglyceride ≤2.5xULN (<300mg/dl). In case one or both of these thresholds are exceeded the patient can only be included after initiation of a statin therapy and when above mentioned values have been achieved.
- INR ≤2.0 Creatinine not more than 2.0 x ULN or creatinine-clearance >40 ml/min (according to Cockcroft-Gault).
- Urine dipstick for proteinuria <2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis should undergo a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours 14. Patients must be available and compliant for treatment and follow-up. Patients registered on this trial must be treated and followed up at the participating or a cooperating center.
Who cannot join
- 1. No documented progression on everolimus plus exemestane 2. Known hypersensitivity reaction to the compounds or incorporated substances 3. Treatment with medroxyprogesteronacetate, megestrolacetate, or high-dose estradiol within 12 weeks of study entry.
- 4. Concurrent immunotherapy or hormonal therapy (contraceptive and/or replacement therapy). Bisphosphonates or denosumab may be continued 5. Life expectancy of less than 3 months. 6. Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy.
- 7. Any ongoing toxicity from prior anti-cancer therapy that is grade 3-4 and/or that is progressing in severity, except alopecia or anemia controlled by growth factors.
- 8. Any previous adverse event grade 3-4 or serious adverse event during treatment with exemestane and everolimus which led to treatment discontinuation 9. Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring anti-anginal medication, previous history of myocardial infarction ≤ 6months, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP >150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease 10. Currently active infection 11. History of other malignancies within the last 5 years which significantly affect the diagnosis, assessment or prognosis of metastatic breast cancer.
- 12. Malabsorption syndrome or insufficient gastrointestinal function, preexisting diagnosis of ulcerative colitis 13. Concurrent treatment with other experimental drugs; participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
- 14. Insufficiently controlled diabetes 15. known HIV infection or chronic hepatitis B or C 16. seriously impaired liver function (Child-Pugh, class C) 17. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures (including severe pulmonary conditions, AIDS and serious active infection and diabetes mellitus).
- 18. Male patients 19. Known HIV infection or chronic or history of hepatitis B or C 20. Seriously impaired liver function (Child-Pugh, class C)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter Randomized, Double Blind, Placebo- Controlled, Phase II Study to Compare Endocrine Treatment Alone Versus Endocrine Treatment With Everolimus in Patients With HR+/HER2- Metastatic Breast Cancer and Progression After Previous Treatment With Exemestane and Everolimus
Everolimus will be given to patients with metastatic breast cancer who already has a progress taking Everolimus but with a change in the endocrine treatment.
Read the detailed description
With continuation of endocrine treatment of breast cancer an adaptive upregulation of different signaling cascades including the PI3K/akt/mTOR pathway results in cell growth stimulation and results in resistance to endocrine therapies. One way to restore endocrine sensitivity is the inhibition of the mTOR pathway in combination with endocrine therapy leading to an increase in PFS compared with endocrine therapy alone. Guidelines recommend the sequential treatment with different endocrine therapies. It therefore appears reasonable to explore if sensitivity can be restored by changing the subsequent endocrine combination partner of Everolimus in case of failure of a combined endocrine-everolimus therapy.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Everolimus, Everolimus-placebo
- Keywords
- everolimus progress exemestane, treated with exemestane and everolimus, progress under this treatment
- 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 Everolimus, Afinitor, RAD-001
Everolimus is given beyond progress (comparison with placebo)
Everolimus-placeboDrug
Also called placebo
Everolimus-placebo
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Everolimus is given beyond progress Receives: Drug: Everolimus |
| Everolimus-placebo | Placebo comparator | Everolimus-placebo is given beyond progress Receives: Drug: Everolimus-placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival
comparison of progression free survival between the two arms: with Everolimus or with Everolimus-placebo
Measured: 3 years
Secondary outcomes (6)
overall survival
comparison of the overall survival between the 2 arms
Measured: 3 years
clinical benefit Rate(CBR)
Clinical Benefit Rate (CBR) is defined as all patients with a complete, partial response and stable disease for at least 24 weeks
Measured: 3 years
chemo-free interval
chemo-free interval is defined as time from last day of chemotherapy in the metastatic setting until first day of next chemotherapy or in patients who have not received chemotherapy in the metastatic setting: the first diagnosis of metastases until start of 1st-line chemotherapy in the metastatic setting.
Measured: 3 years
safety by toxicity
Safety by toxicity grades is defined by the NCI-CTCAE version 4.03
Measured: 3 years
compliance
Compliance will be assessed by the number and reasons of patients whose treatment had to be reduced, delayed or permanently stopped
Measured: 3 years
biological marker
Bone marker estimation in blood and/or urine
Measured: starting in 3 years, biomaterial will be stored, later research possible
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2013 (estimated)
- Study startJul 2013
- Primary completionJul 2014
- Study completionJul 2014
Why it stopped: Study was stopped terminated early due to low recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Sibylle Loibl, Prof., Study chair, Krankenhaus Offenbach
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01773460
- Sponsor's protocol ID
- GBG 76
- Acronym
- Evelyn
- Status last verified
- Feb 2016
- First submitted
- 15 Jan 2013
- Last updated
- 10 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized, Double Blind, Placebo- Controlled, Phase II Study to Compare Endocrine Treatment Alone Versus Endocrine Treatment With Everolimus in Patients With HR+/HER2- Metastatic Breast Cancer and Progression After Previous Treatment With Exemestane and Everolimus
- ClinicalTrials.gov ID
- NCT01773460
- Acronym / sponsor ID
- Evelyn / GBG 76
- Conditions
- Metastatic Breast Cancer
- Keywords
- everolimus progress exemestane, treated with exemestane and everolimus, progress under this treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was stopped terminated early due to low recruitment.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jul 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 23 Jan 2013 (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.
Everolimus will be given to patients with metastatic breast cancer who already has a progress taking Everolimus but with a change in the endocrine treatment.
Detailed description
With continuation of endocrine treatment of breast cancer an adaptive upregulation of different signaling cascades including the PI3K/akt/mTOR pathway results in cell growth stimulation and results in resistance to endocrine therapies. One way to restore endocrine sensitivity is the inhibition of the mTOR pathway in combination with endocrine therapy leading to an increase in PFS compared with endocrine therapy alone. Guidelines recommend the sequential treatment with different endocrine therapies. It therefore appears reasonable to explore if sensitivity can be restored by changing the subsequent endocrine combination partner of Everolimus in case of failure of a combined endocrine-everolimus therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: EverolimusEverolimus is given beyond progress |
| Everolimus-placebo | Placebo comparator | Drug: Everolimus-placeboEverolimus-placebo is given beyond progress |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- 2. Complete baseline documentation must be submitted via the web-based data collection system MedCODES® to the GBG Forschungs GmbH.
- 3. Histological confirmed hormone receptor positive (HR+); HER2-negative carcinoma of the breast. Every effort should be made to make paraffin embedded tissue or slides from the original tumor and/or from metastatic tissue available for confirmation of diagnosis and additional translational research.
- 4. Postmenopausal women 5. HER2-negative, hormone-receptor-positive, locally advanced or metastatic stage of disease not amenable to curative treatment by surgery or radiotherapy alone.
- 6. No indication for chemotherapy 7. Patients must have either measurable or non-measurable target lesions according to RECIST criteria. Complete staging work-up within 4 weeks prior to registration including chest and abdominal CT scan or MRI (exceptionally chest X-ray and abdominal ultrasound), and bone scan. Further tests have to be performed according to RECIST or as clinically indicated.
Key exclusion criteria (7 listed)
- 1. No documented progression on everolimus plus exemestane 2. Known hypersensitivity reaction to the compounds or incorporated substances 3. Treatment with medroxyprogesteronacetate, megestrolacetate, or high-dose estradiol within 12 weeks of study entry.
- 4. Concurrent immunotherapy or hormonal therapy (contraceptive and/or replacement therapy). Bisphosphonates or denosumab may be continued 5. Life expectancy of less than 3 months. 6. Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy.
- 7. Any ongoing toxicity from prior anti-cancer therapy that is grade 3-4 and/or that is progressing in severity, except alopecia or anemia controlled by growth factors.
- 8. Any previous adverse event grade 3-4 or serious adverse event during treatment with exemestane and everolimus which led to treatment discontinuation 9. Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring anti-anginal medication, previous history of myocardial infarction ≤ 6months, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension (i.e. BP >150/100 mmHg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease 10. Currently active infection 11. History of other malignancies within the last 5 years which significantly affect the diagnosis, assessment or prognosis of metastatic breast cancer.
- 12. Malabsorption syndrome or insufficient gastrointestinal function, preexisting diagnosis of ulcerative colitis 13. Concurrent treatment with other experimental drugs; participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
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: Everolimus, Afinitor, RAD-001Everolimus is given beyond progress (comparison with placebo) | Drug | Everolimus |
| Everolimus-placeboAlso: placeboEverolimus-placebo | Drug | Everolimus-placebo |
Primary outcome
progression free survival
Time frame: 3 years
comparison of progression free survival between the two arms: with Everolimus or with Everolimus-placebo
6 secondary outcomes
overall survival
Time frame: 3 years
clinical benefit Rate(CBR)
Time frame: 3 years
chemo-free interval
Time frame: 3 years
safety by toxicity
Time frame: 3 years
compliance
Time frame: 3 years
biological marker
Time frame: starting in 3 years, biomaterial will be stored, later research possible
Results and safety
The study was stopped early (reason given: Study was stopped terminated early due to low recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
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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.
Sibylle Loibl, Prof. study chair
Krankenhaus Offenbach
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Everolimus in people with Metastatic Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
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 21 inclusion and 7 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: stopped early, as of the sponsor's last update on 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Study was stopped terminated early due to low recruitment.). Results are not available in the source record.
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 (time frame: 3 years). 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 10 Feb 2016.