Metastatic Breast CancerPhase 2LEONCT02344550
Study of GnRH-A [Leuprorelin(Lorelin Depot] Plus Leterozole +/- Everolimus for Premenopausal Women With Metastatic Breast Cancer
A Phase 2 study testing Everolimus(afinitor), Letrozole and Leuprolide(Lorelin Depot) in people with Metastatic Breast Cancer, run by Asan Medical Center at 1 site in South Korea.
Trial summary
The purpose of this study is to evaluate the efficacy of addition of everolimus to letrozole with LHRH agonist in premenopausal metastatic breast cancer patients who failed to tamoxifen treatment. Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Everolimus(afinitor), Letrozole and Leuprolide(Lorelin Depot)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 137 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jan 2014to Oct 2018
- Phase
- Phase 2
- 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 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 20 years
- Histologically or cytologically confirmed, HER-2 negative breast cancer with recurrent or metastatic disease
- No HER2 overexpressing breast cancer
- Premenopausal status, defined as either
- ER and/or PR positive
- Progressive disease on tamoxifen treatment or sequential or combined treatment of tamoxifen and GnRH agonist as a palliative or an adjuvant endocrine treatment
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- Duration of tamoxifen treatment should be at least 3 months or more
- No prior treatment with an aromatase inhibitor or inactivator or fulvestrant, or mTOR inhibitors
- One line of chemotherapy in metastatic setting is permitted
- ECOG performance status 0,1 or 2
- At least one measurable lesion or mainly lytic bone lesions in the absence of measurable disease
- Adequate hematologic, liver and kidney function
Who cannot join
- Pregnant women or patients in lactation
- More than one line of prior chemotherapy for metastatic breast cancer
- GnRH agonist with tamoxifen treatment within 2 weeks.
- Active malignancy other than breast cancer, in situ carcinoma of the cervix, controlled resected thyroid well differentiated carcinoma or non-melanomatous skin cancer in the past 5 years
- Active cardiovascular disease such as angina, ventricular tachycardia, uncontrolled hypertension
- Active uncontrolled infection
Show all 10Show fewer
- Symptomatic brain metastases
- Lymphangitic carcinomatosis involving >50% of the lungs
- Evidence of metastases involving more than one third of the liver on sonogram or CT
- Patients not able or unwilling to give informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ovarian Suppression Plus Letrozole Plus Everolimus for Hormone Receptor-Positive, Tamoxifen and Ovarian Suppression Pretreated, Premenopausal Women With Recurrent or Metastatic Breast Cancer[LEO]
The purpose of this study is to evaluate the efficacy of addition of everolimus to letrozole with LHRH agonist in premenopausal metastatic breast cancer patients who failed to tamoxifen treatment.
Read the detailed description
Endocrine therapy is the cornerstone of treatment for patients with hormone receptor (HR)-positive advanced breast cancer. The selection of endocrine agents takes account of the menopausal status, the type of previous adjuvant endocrine treatment, the disease free interval and past medical history1.
The goal of endocrine treatment is to block or interfere with the function of estrogen or progesterone. The major source of estrogen in premenopausal women is the ovaries. In premenopausal women with HR-positive advanced breast cancer, tamoxifen, ovarian function suppression or a combination of those have been used. Unfortunately, not all patients have a response to first-line endocrine therapy, and even patients who have a response will eventually become resistant. Patients experiencing disease progression with a first-line endocrine therapy may benefit from other endocrine agents, such as aromatase inhibitors (steroidal or nonsteroidal) and the estrogen receptor (ER) antagonist2-5. Aromatase inhibitors combined with luteinizing hormone-releasing hormone (LHRH) analogs or ovarian ablation are also a feasible treatment modality for premenopausal patients with HR-positive advanced breast cancer6.
An emerging mechanism of endocrine resistance in aberrant signaling through the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway7-9. Growing evidence supports a close interaction between the mTOR pathway and ER signaling. A substrate of mTOR complex 1 (mTORC1), called S6 kinase 1, phosphorylates the activation function domain 1 of ER, which is responsible for ligand-independent receptor activation10. Everolimus is a sirolimus derivative that inhibits mTOR through allosteric binding to mTORC111. In preclinical models, the use of everolimus in combination with aromatase inhibitors results in synergistic inhibition of the proliferation and induction of apoptosis12. In a randomized, phase 2 study comparing neoadjuvant everolimus plus letrozole with letrozole alone in patients with newly diagnosed ER-positive breast cancer, the response rate for the combination was higher than that for letrozole alone13. Recently, the Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study showed that the addition of everolimus to exemestane significantly improved progression-free survival, with observed medians of 6.9 and 2.8 months, corresponding to a 57% reduction in the hazard ratio14.
Based on this rationale, the investigators introduced randomized trial to evaluate the efficacy of addition of everolimus to letrozole with LHRH agonist in premenopausal metastatic breast cancer patients who failed to tamoxifen treatment.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Everolimus(afinitor), Letrozole, Leuprolide(Lorelin Depot)
- Keywords
- metastatic breast cancer, HER2 negative, hormone-receptor positive
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus(afinitor)Drug
Also called Afinitor
Everolimus 10mg p.o. daily
LetrozoleDrug
Also called Femara
Letrozole 2.5 mg p.o. daily
Leuprolide(Lorelin Depot)Drug
Also called Leuprorelin (Dongkook Pharm Co Ltd)
Leuprorelin (Lorelin Depot)3.75 mg SC in every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Everolimus arm | Experimental | Everolimus 10mg p.o. daily Letrozole 2.5 mg p.o. daily Leuprorelin (Leuprolide) 3.75mg SC every 4 weeks Receives: Drug: Everolimus(afinitor); Drug: Letrozole; Drug: Leuprolide(Lorelin Depot) |
| Control arm | Active comparator | Letrozole 2.5 mg p.o. daily Leuprorelin (Leuprolide) 3.75mg SC every 4 weeks Receives: Drug: Letrozole; Drug: Leuprolide(Lorelin Depot) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
At time disease progression
Measured: Participants will be followed every 8 weeks , up to 12 Months
Secondary outcomes (1)
Overall Response rate
At time disease evaluation
Measured: Participants will be followed every 8 weeks, up to 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2015 (estimated)
- Study startJan 2014
- Primary completionOct 2018
- Study completionOct 2018
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.
- More trials run by Asan Medical CenterThe 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
- None (open label)
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sung-Bae Kim, Asan Medical Center
- Investigators
- Sung-Bae Kim, M.D., Ph D., Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02344550
- Sponsor's protocol ID
- AMC 2013-0720
- Other IDs
- AMC
- Acronym
- LEO
- Status last verified
- Jul 2020
- First submitted
- 7 May 2014
- Last updated
- 30 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovarian Suppression Plus Letrozole Plus Everolimus for Hormone Receptor-Positive, Tamoxifen and Ovarian Suppression Pretreated, Premenopausal Women With Recurrent or Metastatic Breast Cancer[LEO]
- ClinicalTrials.gov ID
- NCT02344550
- Acronym / sponsor ID
- LEO / AMC 2013-0720
- Conditions
- Metastatic Breast Cancer
- Keywords
- metastatic breast cancer, HER2 negative, hormone-receptor positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 26 Jan 2015 (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 purpose of this study is to evaluate the efficacy of addition of everolimus to letrozole with LHRH agonist in premenopausal metastatic breast cancer patients who failed to tamoxifen treatment.
Detailed description
Endocrine therapy is the cornerstone of treatment for patients with hormone receptor (HR)-positive advanced breast cancer. The selection of endocrine agents takes account of the menopausal status, the type of previous adjuvant endocrine treatment, the disease free interval and past medical history1.
The goal of endocrine treatment is to block or interfere with the function of estrogen or progesterone. The major source of estrogen in premenopausal women is the ovaries. In premenopausal women with HR-positive advanced breast cancer, tamoxifen, ovarian function suppression or a combination of those have been used. Unfortunately, not all patients have a response to first-line endocrine therapy, and even patients who have a response will eventually become resistant. Patients experiencing disease progression with a first-line endocrine therapy may benefit from other endocrine agents, such as aromatase inhibitors (steroidal or nonsteroidal) and the estrogen receptor (ER) antagonist2-5. Aromatase inhibitors combined with luteinizing hormone-releasing hormone (LHRH) analogs or ovarian ablation are also a feasible treatment modality for premenopausal patients with HR-positive advanced breast cancer6.
An emerging mechanism of endocrine resistance in aberrant signaling through the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway7-9. Growing evidence supports a close interaction between the mTOR pathway and ER signaling. A substrate of mTOR complex 1 (mTORC1), called S6 kinase 1, phosphorylates the activation function domain 1 of ER, which is responsible for ligand-independent receptor activation10. Everolimus is a sirolimus derivative that inhibits mTOR through allosteric binding to mTORC111. In preclinical models, the use of everolimus in combination with aromatase inhibitors results in synergistic inhibition of the proliferation and induction of apoptosis12. In a randomized, phase 2 study comparing neoadjuvant everolimus plus letrozole with letrozole alone in patients with newly diagnosed ER-positive breast cancer, the response rate for the combination was higher than that for letrozole alone13. Recently, the Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study showed that the addition of everolimus to exemestane significantly improved progression-free survival, with observed medians of 6.9 and 2.8 months, corresponding to a 57% reduction in the hazard ratio14.
Based on this rationale, the investigators introduced randomized trial to evaluate the efficacy of addition of everolimus to letrozole with LHRH agonist in premenopausal metastatic breast cancer patients who failed to tamoxifen treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus arm | Experimental | Drug: Everolimus(afinitor), Drug: Letrozole, Drug: Leuprolide(Lorelin Depot)Everolimus 10mg p.o. daily Letrozole 2.5 mg p.o. daily Leuprorelin (Leuprolide) 3.75mg SC every 4 weeks |
| Control arm | Active comparator | Drug: Letrozole, Drug: Leuprolide(Lorelin Depot)Letrozole 2.5 mg p.o. daily Leuprorelin (Leuprolide) 3.75mg SC every 4 weeks |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 20 years
- Histologically or cytologically confirmed, HER-2 negative breast cancer with recurrent or metastatic disease
- No HER2 overexpressing breast cancer
- Premenopausal status, defined as either
- ER and/or PR positive
Key exclusion criteria (10 listed)
- Pregnant women or patients in lactation
- More than one line of prior chemotherapy for metastatic breast cancer
- GnRH agonist with tamoxifen treatment within 2 weeks.
- Active malignancy other than breast cancer, in situ carcinoma of the cervix, controlled resected thyroid well differentiated carcinoma or non-melanomatous skin cancer in the past 5 years
- Active cardiovascular disease such as angina, ventricular tachycardia, uncontrolled hypertension
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 |
|---|---|---|
| Everolimus(afinitor)Also: AfinitorEverolimus 10mg p.o. daily | Drug | Everolimus arm |
| LetrozoleAlso: FemaraLetrozole 2.5 mg p.o. daily | Drug | Control arm, Everolimus arm |
| Leuprolide(Lorelin Depot)Also: Leuprorelin (Dongkook Pharm Co Ltd)Leuprorelin (Lorelin Depot)3.75 mg SC in every 4 weeks | Drug | Control arm, Everolimus arm |
Primary outcome
Progression free survival (PFS)
Time frame: Participants will be followed every 8 weeks , up to 12 Months
At time disease progression
1 secondary outcome
Overall Response rate
Time frame: Participants will be followed every 8 weeks, up to 12 Months
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 30 Jul 2020.
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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.
Sung-Bae Kim, M.D., Ph D. principal investigator
Asan Medical Center
1 site 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(afinitor), Letrozole and Leuprolide(Lorelin Depot) in people with Metastatic Breast Cancer, run by Asan Medical Center at 1 site in South Korea.
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 10 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 30 Jul 2020. 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 South Korea. 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?
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?
Progression free survival (PFS) (time frame: Participants will be followed every 8 weeks , up to 12 Months). 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 30 Jul 2020.