Actively Recruiting
Lenvatinib+Letrozole Versus Fulvestrant in Metastatic ER+/HER2- Breast Cancer, Post Progression on Al + CDK4/6 Inhibitor
Led by National University Hospital, Singapore · Updated on 2025-07-25
120
Participants Needed
1
Research Sites
291 weeks
Total Duration
On this page
Sponsors
N
National University Hospital, Singapore
Lead Sponsor
E
Eisai Co., Ltd.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Based on the results of the phase Ib/II study, the investigators hypothesize that combining a RET inhibitor lenvatinib with endocrine therapy letrozole improves objective response and progression-free survival compared to fulvestrant alone in the second line setting in patients who have progressed on first line endocrine therapy incorporating a CDK4/6 inhibitor. Letrozole and fulvestrant are anti-hormonal drugs that have been proven to have activity and are considered standard therapies for hormone receptor positive breast cancer. The purpose of this study is to determine if the combination therapy of letrozole (an anti-hormonal drug) and lenvatinib (a targeted therapy), when compared to another anti-hormonal drug fulvestrant, is effective in patients with hormone receptor positive breast cancer. Preliminary studies have shown that approximately 50-60% of hormone receptor positive breast cancers over-express RET, and may therefore respond to treatment by a drug that blocks the RET pathway. An earlier study conducted at the National University Cancer Institute, Singapore (NCIS) on the combination of letrozole and Lenvatinib has shown promising results. Among patients in whom hormonal therapy and a CDK4/6 inhibitor no longer worked, about one-quarter of patients had meaningful disease control. The study also showed that patients tolerated the combination of Lenvatinib and letrozole well with manageable side effects. Based on the promising findings from the earlier study, this study seeks to compare the effectiveness of lenvatinib plus letrozole with another standard anti-hormone treatment drug called fulvestrant. In addition, investigators are studying how body reacts to the treatment as well as studying gene and protein changes in the tumour in response to treatment, which may in the future, help us tailor drug treatment for individual patients according to the patient's and/or the tumour's genetic or protein make-up.
CONDITIONS
Official Title
Lenvatinib+Letrozole Versus Fulvestrant in Metastatic ER+/HER2- Breast Cancer, Post Progression on Al + CDK4/6 Inhibitor
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Female, age 18 years or older
- Histologic or cytologic diagnosis of breast carcinoma
- Estrogen receptor positive, defined as 1% or more on immunohistochemical staining
- Disease progressed on first-line palliative endocrine therapy plus CDK4/6 inhibitor as immediate prior endocrine therapy
- Only one prior line of endocrine therapy in metastatic setting
- No more than one prior line of chemotherapy in metastatic setting
- Measurable disease by RECIST criteria
- ECOG performance status 0 or 1
- Estimated life expectancy of at least 12 weeks
- Adequate organ function including bone marrow, liver, and kidneys
- Normal thyroid function or thyroid dysfunction that is optimally controlled
- Post-menopausal women or pre-menopausal women with medical ovarian suppression and post-menopausal hormone levels
- Signed informed consent from patient or legal representative
You will not qualify if you...
- HER2 positive tumors
- Treatment with any investigational drug within the last 30 days
- Prior therapy with fulvestrant
- Concurrent use of other tumor therapies including chemotherapy, hormonal therapy, or immunotherapy
- Major surgery within 28 days before study drug administration
- Active infection compromising ability to tolerate therapy
- Pregnancy or breastfeeding
- Serious medical disorders compromising safety or study completion
- Non-healing wounds
- Poorly controlled diabetes mellitus
- Clinically detectable second primary malignancy at enrollment
- Uncontrolled or symptomatic brain metastases or brain metastases requiring steroids
- History of significant neurological or mental disorders including seizures or dementia
- Uncontrolled blood pressure despite optimized antihypertensive treatment
- Proteinuria grade 2 or higher (protein >1.0g/24h)
- Significant cardiovascular impairment including heart failure NYHA class greater than II, unstable angina, recent myocardial infarction or stroke, or arrhythmia needing treatment
- Bleeding or thrombotic disorders, active gastrointestinal bleeding, use of anticoagulants requiring therapeutic INR monitoring, or risk of severe hemorrhage
- Baseline QTc interval greater than 480ms persisting despite correction of abnormalities or discontinuation of QTc-prolonging medications
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Trial Site Locations
Total: 1 location
1
Nationa University Hospital
Singapore, Singapore
Actively Recruiting
Research Team
S
Soo Chin Lee
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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