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Lenvatinib+Letrozole Versus Fulvestrant in Metastatic ER+/HER2- Breast Cancer, Post Progression on Al + CDK4/6 Inhibitor

NCT05181033 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 120

Last updated 2025-07-25

No results posted yet for this study

Summary

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

Interventions

DRUG

Lenvatinib + Letrozole

Patient will receive letrozole 2.5mg daily plus lenvatinib 14mg daily until disease progression/unacceptable toxicity. Patient review, safety evaluations, thyroid function monitoring and urine dipstick will be done. Toxicities will be graded using NCI CTCAE toxicity grading vs 4.0. Patient should be discontinued if drug cannot be resumed within 28 days due to toxicities. Drugs should be withheld when subject has imminent risk to develop hypertensive crisis/has significant risk factors for severe complications of uncontrolled hypertension. Drugs can be resumed once patient received same hypertensive medications for at least 48 hours and the BP is controlled. Lenvatinib should be withheld for at least 1 week prior to elective surgery, at least 2 weeks after major surgery, until adequate wound healing. For risk of ONJ, oral dental examination and preventive dentistry should be considered prior to lenvatinib intake. There is no dose modifications for letrozole.

DRUG

Fulvestrant

Patients will be treated with Fulvestrant 500mg injections that are administered into the muscles (intramuscularly). This is injected at 2-weekly interval for the first 3 doses, followed by 4-weekly interval dosing.

Sponsors & Collaborators

  • Eisai Co., Ltd.

    collaborator INDUSTRY

  • National University Hospital, Singapore

    lead OTHER

Principal Investigators

  • Soo Chin Lee · National University Hospital, Singapore

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
99 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-12-27
Primary Completion
2027-08-31
Completion
2027-08-31

Countries

  • Singapore

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05181033 on ClinicalTrials.gov