Ignite Creation Date:
2025-12-25 @ 5:02 AM
Ignite Modification Date:
2026-01-07 @ 1:44 PM
Study NCT ID:
NCT02562118
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-09-25
First Post:
2015-09-08
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Neoadjuvant Lenvatinib Combined With Letrozole in Hormone Receptor Positive Breast Cancer
Sponsor:
National University Hospital, Singapore
Organization:
Study Overview
Official Title:
Phase Ib Followed by Phase II Study of Pre-operative Treatment With Lenvatinib Combined With Letrozole in Post-menopausal Women With Newly Diagnosed Hormone Receptor Positive Breast Cancer With Measurable Primary Breast Tumor
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a single-centre study comprising two phases: a lead-in phase Ib and a phase II randomized portion.
Lead-in Phase Ib study A lead-in phase I study will be built into this protocol to confirm the dose of lenvatinib that can safely be combined with letrozole.
We expect that the optimal phase II dose level will be determined after recruiting 12-18 subjects into phase Ib. This dose level will be the one to be tested in the phase II portion of the study.
Phase II open label study In this part of the study, eligible patients will be treated with single agent lenvatinib at the phase II recommended dose for 2 weeks, followed by lenvatinib combined with letrozole 2.5mg daily for 12 weeks.
A total of 30 patients with ER positive breast cancer and measurable primary tumor will be enrolled over a period of 24-30 months
Lead-in Phase Ib study A lead-in phase I study will be built into this protocol to confirm the dose of lenvatinib that can safely be combined with letrozole.
We expect that the optimal phase II dose level will be determined after recruiting 12-18 subjects into phase Ib. This dose level will be the one to be tested in the phase II portion of the study.
Phase II open label study In this part of the study, eligible patients will be treated with single agent lenvatinib at the phase II recommended dose for 2 weeks, followed by lenvatinib combined with letrozole 2.5mg daily for 12 weeks.
A total of 30 patients with ER positive breast cancer and measurable primary tumor will be enrolled over a period of 24-30 months
Detailed Description:
Hypothesis:
We hypothesize that combining a RET inhibitor such as lenvatinib with endocrine therapy may potentiate anti-tumor effects in ER+ breast cancers in the clinic. Given that RET inhibition is the primary mechanism of action of lenvatinib, we further hypothesize that RET expression in the breast tumor may be a biomarker that predicts for better response to the combination of a RET inhibitor and endocrine therapy in both a neoadjuvant (Part A) and a metastatic (Part B) setting.
Primary Objectives
1. To confirm the dose of lenvatinib that can be safely combined with letrozole in the lead-in Phase Ib part of the study.
2. Part A (For patients with non-metastatic breast cancer undergoing neoadjuvant treatment) : To determine the overall clinical response (measured by ultrasound) and pathological complete response rate after 2 weeks of neoadjuvant single agent lenvatinib followed by 12 weeks of letrozole combined with lenvatinib and compare with historical controls treated with single agent letrozole.
3. Part B (For patients with metastatic breast cancer and who have tumor lesion that can be serially biopsied safely): to determine the clinical response (measured by RECIST criteria) after 2 weeks of single agent lenvatinib followed by continuous dual therapy of lenvatinib and letrozole, until time of progression or intolerability.
Secondary Objectives
1. To evaluate the overall biological effects (Ki67 changes, histological response, apoptosis, RET and downstream targets such as AKT and ERK) of 2 weeks of single agent lenvatinib, and of letrozole + lenvatinib, in ER positive breast cancer, respectively.
2. To identify biological predictors for treatment response to letrozole + lenvatinib in ER positive breast cancer using pharmacokinetics, pharmacogenetics, genomics and proteomics strategies.
3. To compare the following parameters between RET positive versus RET negative, ER positive breast cancer:
* Part A :
i. Clinical response (measured by ultrasound) and biological effects of 2 weeks of single agent lenvatinib, ii. Clinical response (measured by ultrasound) and biological effects after 2 weeks of single agent lenvatinib followed by 12 weeks of letrozole combined with lenvatinib
-Part B : i. Clinical response measured by RECIST criteria after 2 weeks of single agent lenvatinib followed by letrozole combined with lenvatinib ii. Progression-free and overall survival with letrozole combined with lenvatinib
We hypothesize that combining a RET inhibitor such as lenvatinib with endocrine therapy may potentiate anti-tumor effects in ER+ breast cancers in the clinic. Given that RET inhibition is the primary mechanism of action of lenvatinib, we further hypothesize that RET expression in the breast tumor may be a biomarker that predicts for better response to the combination of a RET inhibitor and endocrine therapy in both a neoadjuvant (Part A) and a metastatic (Part B) setting.
Primary Objectives
1. To confirm the dose of lenvatinib that can be safely combined with letrozole in the lead-in Phase Ib part of the study.
2. Part A (For patients with non-metastatic breast cancer undergoing neoadjuvant treatment) : To determine the overall clinical response (measured by ultrasound) and pathological complete response rate after 2 weeks of neoadjuvant single agent lenvatinib followed by 12 weeks of letrozole combined with lenvatinib and compare with historical controls treated with single agent letrozole.
3. Part B (For patients with metastatic breast cancer and who have tumor lesion that can be serially biopsied safely): to determine the clinical response (measured by RECIST criteria) after 2 weeks of single agent lenvatinib followed by continuous dual therapy of lenvatinib and letrozole, until time of progression or intolerability.
Secondary Objectives
1. To evaluate the overall biological effects (Ki67 changes, histological response, apoptosis, RET and downstream targets such as AKT and ERK) of 2 weeks of single agent lenvatinib, and of letrozole + lenvatinib, in ER positive breast cancer, respectively.
2. To identify biological predictors for treatment response to letrozole + lenvatinib in ER positive breast cancer using pharmacokinetics, pharmacogenetics, genomics and proteomics strategies.
3. To compare the following parameters between RET positive versus RET negative, ER positive breast cancer:
* Part A :
i. Clinical response (measured by ultrasound) and biological effects of 2 weeks of single agent lenvatinib, ii. Clinical response (measured by ultrasound) and biological effects after 2 weeks of single agent lenvatinib followed by 12 weeks of letrozole combined with lenvatinib
-Part B : i. Clinical response measured by RECIST criteria after 2 weeks of single agent lenvatinib followed by letrozole combined with lenvatinib ii. Progression-free and overall survival with letrozole combined with lenvatinib
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2015/00411 | OTHER | NHG DSRB | View |