Advanced or Metastatic Breast CancerPhase 1LeeBLetNCT02154776
Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole in HR+, HER2-negative Post-menopausal Women With Advanced Breast Cancer.
A Phase 1 study testing LEE011, Buparlisib and Letrozole in people with Advanced or Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 6 sites in 2 countries.
Trial summary
This is a multi-center, open-label, non-randomized, phase I study Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced or Metastatic Breast Cancer
- What is being tested?
- LEE011, Buparlisib and Letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 27 Jun 2014to 26 Oct 2016
- Phase
- Phase 1
- 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
- Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease.
- Patient is postmenopausal.
- Patient may have received ≤ 2 lines of chemotherapy for metastatic or recurrent breast cancer in the dose-escalation phase.
- Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
- Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
- Patient must have either:
- Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion
Who cannot join
- Patient who received any CDK4/6 or PI3K inhibitor.
- Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
- History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry
- History of documented congestive heart failure (New York Heart Association functional classification III-IV)
- Documented cardiomyopathy
- Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
Show all 14Show fewer
- History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.
- On screening, any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval >109 msec, or QTcF >450 msec.
- Systolic blood pressure >160 or <90 mmHg
- Patient is currently receiving any of the following medications:
- That are known strong inducers or inhibitors of CYP3A4.
- That have a known risk to prolong the QT interval or induce Torsades de Pointes.
- That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.
- Certain scores on an anxiety and depression mood questionnaires
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States5 sites
Medical University of South Carolina SC
Charleston, South Carolina, 29425
Horizon Oncology Center SC
Lafayette, Indiana, 47905
University of California at Los Angeles UCLA SC
Los Angeles, California, 90095
University of Utah / Huntsman Cancer Institute SC-3
Salt Lake City, Utah, 84103
South Texas Accelerated Research Therapeutics SC
San Antonio, Texas, 78922
About this study
Official title: A Phase 1 Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole for the Treatment of HR+, HER2-negative Post-menopausal Women With Locally Advanced or Metastatic Breast Cancer.
This is a multi-center, open-label, non-randomized, phase I study
- Conditions
- Advanced or Metastatic Breast Cancer
- Being tested
- LEE011, Buparlisib, Letrozole
- Keywords
- LEE011,, buparlisib,, letrozole,, HR +,, HER2 - negative,, post-menopausal,, breast cancer,, CDK 4/6,, PI3K,, MTD
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEE011Drug
3 weeks on and 1 week off
BuparlisibDrug
daily
LetrozoleDrug
2.5 mg daily;
| Study group | Role | What they receive |
|---|---|---|
| LEE011 + buparlisib + letrozole | Experimental | open label, dose escalation evaluating max tolerated dose of the triple combination Receives: Drug: LEE011; Drug: Buparlisib; Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of LEE011, buparlisib, and letrozole in a 28 day cycle
Measured: 28 days
Safety and tolerability of the combination of LEE011, buparlisib, and letrozole
Dose Expansion Phase: Incidence of AEs, SAEs (overal and severity), laboratory abnormalities, ECG, vital, dose interteruptions, dose reductions, and dose intensity as a measure of safety and tolerability.
Measured: approximately 25 months
Secondary outcomes (5)
Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole
Dose Escalation Phase: Incidence of AEs, SAEs (overall and severity), laboratory abnormalities, ECG, vital, dose interterruptions, dose reductions, and dose intensity as a measure of safety and tolerability.
Measured: approximately 25 months
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
Dose Escalation Phase: When given in combination as well any other clinically significant metabolites that may be identified
Measured: approximately 25 months
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
Dose Expansion Phase: When given in combination as well as any other clinically significant metabolites that may be identified
Measured: approximately 25 months
Disease control rate
Dose Expansion Phase: Proportion of patients with the best overall response of CR (complete response), PR (partial response), or SD (stable disease)
Measured: approximately 25 months
PFS (progression free survival)
Dose Expansion Phase: Time from date of start of treatment to date of first documented progression or death due to any cause.
Measured: approximately 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2014 (estimated)
- Study start27 Jun 2014
- Primary completion26 Oct 2016
- Study completion26 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or 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 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 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
- NCT02154776
- Sponsor's protocol ID
- CLEE011A2112C
- Acronym
- LeeBLet
- Status last verified
- Jul 2018
- First submitted
- 28 May 2014
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole for the Treatment of HR+, HER2-negative Post-menopausal Women With Locally Advanced or Metastatic Breast Cancer.
- ClinicalTrials.gov ID
- NCT02154776
- Acronym / sponsor ID
- LeeBLet / CLEE011A2112C
- Conditions
- Advanced or Metastatic Breast Cancer
- Keywords
- LEE011,, buparlisib,, letrozole,, HR +,, HER2 - negative,, post-menopausal,, breast cancer,, CDK 4/6,
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Jun 2014 (actual)
- Primary completion
- 26 Oct 2016 (actual)
- Study completion
- 26 Oct 2016 (actual)
- First posted
- 3 Jun 2014 (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.
This is a multi-center, open-label, non-randomized, phase I study
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LEE011 + buparlisib + letrozole | Experimental | Drug: LEE011, Drug: Buparlisib, Drug: Letrozoleopen label, dose escalation evaluating max tolerated dose of the triple combination |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease.
- Patient is postmenopausal.
- Patient may have received ≤ 2 lines of chemotherapy for metastatic or recurrent breast cancer in the dose-escalation phase.
- Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
- Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
Key exclusion criteria (14 listed)
- Patient who received any CDK4/6 or PI3K inhibitor.
- Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
- Systolic blood pressure >160 or <90 mmHg
- Patient is currently receiving any of the following medications:
- Certain scores on an anxiety and depression mood questionnaires
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 |
|---|---|---|
| LEE0113 weeks on and 1 week off | Drug | LEE011 + buparlisib + letrozole |
| Buparlisibdaily | Drug | LEE011 + buparlisib + letrozole |
| Letrozole2.5 mg daily; | Drug | LEE011 + buparlisib + letrozole |
Primary outcome
Incidence of dose-limiting toxicities (DLTs)
Time frame: 28 days
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of LEE011, buparlisib, and letrozole in a 28 day cycle
Safety and tolerability of the combination of LEE011, buparlisib, and letrozole
Time frame: approximately 25 months
Dose Expansion Phase: Incidence of AEs, SAEs (overal and severity), laboratory abnormalities, ECG, vital, dose interteruptions, dose reductions, and dose intensity as a measure of safety and tolerability.
5 secondary outcomes
Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole
Time frame: approximately 25 months
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
Time frame: approximately 25 months
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
Time frame: approximately 25 months
Disease control rate
Time frame: approximately 25 months
PFS (progression free survival)
Time frame: approximately 25 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 19 Dec 2020.
- Results for CLEE011A2112C can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LEE011, Buparlisib and Letrozole in people with Advanced or Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 6 sites in 2 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 7 inclusion and 14 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 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Spain. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Incidence of dose-limiting toxicities (DLTs) (time frame: 28 days). The study lists 2 primary outcomes in all. 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 19 Dec 2020.