OncoMatch/Clinical Trials/NCT05181033
Lenvatinib+Letrozole Versus Fulvestrant in Metastatic ER+/HER2- Breast Cancer, Post Progression on Al + CDK4/6 Inhibitor
Is NCT05181033 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Lenvatinib + Letrozole and Fulvestrant for breast cancer.
Treatment: Lenvatinib + Letrozole · Fulvestrant — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Breast Carcinoma
Biomarker criteria
Required: ESR1 overexpression (>=1% on immunohistochemical staining)
Estrogen receptor positive (defined as >=1% on immunohistochemical staining)
Required: HER2 (ERBB2) wild-type
HER2 negative
Disease stage
Metastatic disease required
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Must have received: endocrine therapy — metastatic
Must have received: cdk4/6 inhibitor — metastatic
Cannot have received: fulvestrant (fulvestrant)
Lab requirements
Blood counts
ANC >=1.5 x 10^9/L, Platelets >=100 x 10^9/L
Kidney function
Creatinine <= 1.5x ULN
Liver function
Bilirubin <= 1.5 x ULN, ALT or AST<= 2.5x ULN, (or <=5 X with liver metastases)
Cardiac function
Significant cardiovascular impairment: history of congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction or stroke within 6 months of first dose of study drug, or cardiac arrhythmia requiring medical treatment at screening [excluded]. Patients with baseline QTc interval >480ms that persists despite correction of electrolyte abnormalities and/or discontinuation of concomitant medications that are known to prolong QTc interval [excluded].
Adequate organ function including the following: Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) >=1.5 x 10^9/L Platelets >=100 x 10^9/L; Hepatic: Bilirubin <= 1.5 x ULN, ALT or AST<= 2.5x ULN, (or <=5 X with liver metastases); Renal: Creatinine <= 1.5x ULN
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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