Breast CancerPhase 2NCT03168074
Phase II Study of Single Agent Lenvatinib
A Phase 2 study testing lenvatinib in people with Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
The Investigators hypothesize that single agent lenvatinib has biological activity in estrogen receptor positive breast cancer, and that the effects are more pronounced in patients with positive RET expression in the tumor. Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- lenvatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSingapore
- Study dates
- 28 Mar 2017to 28 Mar 2021
- Phase
- Phase 2
- 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 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must fulfill ALL the following inclusion criteria
- Female ≥18 years
- Histological or cytological diagnosis of breast carcinoma
- No prior treatment for current breast carcinoma
- Scheduled for upfront definitive breast cancer surgery (breast conserving surgery or mastectomy with or without sentinel lymph node biopsy or axillary lymph node clearance)
- Estrogen receptor positive (>1%)
Show all 20Show fewer
- Adequate bone marrow, renal and liver function
- Adequate organ function including the following:
- Bone marrow:
- Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L
- Platelets >= 100 x 109/L
- Hepatic:
- Bilirubin < = 1.5 x upper limit of normal (ULN),
- ALT or AST < = 2.5x ULN, (or < = 5 X with liver metastases)
- Renal:
- Creatinine < = 1.5x ULN
- Normal thyroid function
- Able to swallow pills
- Able to sign informed consent
- Able to comply with study-related procedures
Who cannot join
- Patients will be excluded from the study for any of the following reasons:
- Scheduled for neoadjuvant systemic therapy
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Treatment within the last 28 days with any investigational drug.
- Major surgery within 28 days of study drug administration.
- Pregnancy.
Show all 12Show fewer
- Breast feeding.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- Poorly controlled diabetes mellitus.
- Second primary malignancy that is clinically detectable at the time of consideration for study enrollment
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
Nationa University Hospital
Singapore
Soo Chin Lee, MBBS, MRCP, +65 6779 5555, Soo_Chin_Lee@nuhs.edu.sg
Soo Chin Lee, MBBS, MRCP
About this study
Official title: A Phase II Window-of-opportunity Study of Single Agent Lenvatinib in Estrogen Receptor Positive Early Stage Breast Cancer
The Investigators hypothesize that single agent lenvatinib has biological activity in estrogen receptor positive breast cancer, and that the effects are more pronounced in patients with positive RET expression in the tumor.
Read the detailed description
Background and Rationale of Study:
- RET and Endocrine Resistance in Breast Cancer RET is an estrogen response gene, and preclinical studies have demonstrated cross talk between RET and ER. Significant interactions between RET and ERα pathways have been described, with increased response to estrogen stimulation observed in the presence of functional RET. RET is associated with resistance to tamoxifen and aromatase inhibitors, and increased RET expression has been demonstrated in hormone resistant cell lines and primary tumors.Combined anti-estrogen and anti-RET therapy in luminal breast cancer had a greater effect on cell growth than either therapy alone. The two classes of drugs have different mechanisms of action; a RET TKI reduced growth through induction of apoptosis, while anti-ERα reduced cell proliferation, forming the biologic basis for dual treatment.Dual therapy with tamoxifen and vandetinib, a RET inhibitor, resulted in greater reduction in tumor growth rate in MCF7 xenografts in mice.RET has been reported to be over-expressed in up to 75% of ER+ breast cancers (n=20), compared to only 10% of ER-negative breast cancers (n=10) in a small study. Recently, the investigators tested 94 archival breast cancer specimens from the National University Hospital, Singapore and found RET over-expression (2-3+) to be present in 59% of ER negative breast cancers (n=39) and 62% of ER positive breast cancers (n=55)
There is limited clinical experience in combining RET inhibitors with endocrine therapy in breast cancer, with only one reported study using vandetanib. In this study, 127 post-menopausal metastatic breast cancer patients with hormone receptor-positive, bone-predominant disease, were randomized to fulvestrant alone versus fulvestrant combined with vandetanib. No differences in clinical benefit rate, progression-free survival, or overall survival, were noted between the two treatment groups. Vandetanib, however, is a less potent inhibitor of RET than lenvatinib. Lenvatinib has been granted orphan drug designation for thyroid cancer by the United States Food and Drug Administration in 2013, but is not being actively developed in breast cancer.
The investigators tested 9 ER+ breast cancer cell lines for RET expression using Western blot, and identified 4 with high expression (BT474, MB361, HCC1419, UACC812), 2 with normal expression (MCF7, CAMA1), and 3 with low expression (T47D, ZR-75-1, BT483). To evaluate the effects of combining lenvatinib with endocrine therapy in ER+ breast cancer cell lines with different RET expression, the investigators performed experiments using 6 cell lines, including 2 with high RET expression (BT474, MB361), 2 with normal RET expression (MCF7, CAMA1), and 2 with low RET expression (T47D, ZR-75-1). IC50 to tamoxifen and lenvatinib alone was established for each cell line, followed by combination therapy at 3 different doses for each drug. Cell apoptosis and proliferation was measured using caspase 3/7 and MTT assays respectively. Preliminary experiments showed lenvatinib to have activity in ER positive breast cancer cell lines, regardless of levels of RET expression. Lenvatinib was at least additive with tamoxifen in all 6 ER positive breast cancer cell lines tested, with the combination resulting in ≥50% cell kill compared to single agent tamoxifen in BT474, CAMA1, and T47D cell lines. These pre-clinical observations suggest the potential role of lenvatinib in combination with endocrine therapy in the treatment of ER positive breast cancers.
Cells were seeded on 96-well plates and after 24 hours, the cells were treated with tamoxifen and lenvatinib simultaneously at different doses (tamoxifen at 0, 1, or 5µM, lenvatinib at 0, 5, 10 µM) and incubated for 72 hours. Cell viability was assessed using CCK-8 assay.
- Preliminary observation of clinical activity of single agent lenvatinib in hormone receptor positive breast cancer
The investigators previously hypothesized that combining a RET inhibitor such as lenvatinib with endocrine therapy may potentiate anti-tumor effects in hormone receptor positive breast cancers. The investigators have recently initiated a study of lenvatinib + letrozole as neoadjuvant therapy in hormone receptor positive breast cancer patients. Eligible patients were treated with two weeks of single agent lenvatinib, followed by 12 weeks of lenvatinib + letrozole. Two patients have been enrolled and the investigators observed tumor reduction of 10-15% on ultrasound after 2 weeks of single agent lenvatinib. To confirm these interesting observations, the investigators intend to treat a larger cohort of patients with newly diagnosed early stage breast cancer who are awaiting definitive breast cancer surgery with approximately 2 weeks of single agent lenvatinib using a window-of-opportunity design, and evaluate tumor response on ultrasound and histological changes from pre- and post-treatment tumor biopsies. This design will allow the investigators to expand the target population for rapid enrollment to achieve a quick signal on biological activity of lenvatinib in human breast cancers in vivo.
- Conditions
- Breast Cancer
- Being tested
- lenvatinib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lenvatinibDrug
Eligible patients will be treated with approximately 2 weeks of single agent lenvatinib (range 10-28 days, depending on the date of breast cancer surgery; last dose of lenvatinib to be administered no later than 48 hours before surgery in patients who are planned to receive ≤14 days lenvatinib, and no later than 120 hours before surgery in patients who are planned to receive 15-28 days lenvatinib).Tissue sections from the pre-treatment and post-treatment tumor will be collected for biomarker analysis. Pre- and post-treatment ultrasound will be used to document the size of the target lesions.
| Study group | Role | What they receive |
|---|---|---|
| lenvatinib | Experimental | Eligible patients will be treated with approximately 2 weeks of single agent lenvatinib (range 10-28 days, depending on the date of breast cancer surgery; last dose of lenvatinib to be administered no later than 48 hours before surgery in patients who are planned to receive ≤14 days lenvatinib, and no later than 120 hours before surgery in patients who are planned to receive 15-28 days lenvatinib). Receives: Drug: lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
To evaluate Ki67 changes. The Ki-67 protein is a cellular marker for proliferation. It is strictly associated with cell proliferation. Ki67 has been shown to be a surrogate marker of biological activity and treatment response in estrogen receptor positive breast cancer treated with endocrine therapy.
Measured: after 10-28 days of single agent lenvatinib
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
To evaluate histological response such as the improvement in the appearance of microscopic tissue specimens after treatment with lenvatinib. The improved appearance of biopsy specimens after treatment often suggests the patient's prognosis will improve as well.
Measured: after 10-28 days of single agent lenvatinib
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
To evaluate apoptosis. Apoptosis is the death of cells which occurs as a normal and controlled part of an organism's growth or development. The presence of apoptosis indicates anti-cancer effects.
Measured: after 10-28 days of single agent lenvatinib
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
To evaluate RET. RET is an estrogen response gene. RET is associated with resistance to tamoxifen and aromatase inhibitors, and increased RET expression has been demonstrated in hormone resistant cell lines and primary tumors.
Measured: after 10-28 days of single agent lenvatinib
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
To evaluate downstream targets such as AKT. AKT /protein kinase B (PKB) is a cardinal node in diverse signaling cascades important in both normal cellular physiology and various disease states. AKT signaling regulates cell proliferation and survival, cell growth (size), glucose metabolism, cell motility and angiogenesis. Aberrant regulation of these processes results in cellular perturbations considered hallmarks of cancer, and numerous studies testify to the frequent hyperactivation of AKT signaling in many human cancer.
Measured: after 10-28 days of single agent lenvatinib
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
To evaluate downstream targets such as ERK. ERK is Extracellular signal-regulated kinase. Deregulation of ERK signalling pathway is linked to many other aspects of the tumour phenotype.
Measured: after 10-28 days of single agent lenvatinib
Secondary outcomes (4)
Changes in the primary tumor dimensions
to obtain the percentage change in primary breast tumor dimension measured by ultrasound
Measured: after 10-28 days of single agent lenvatinib
The proportion of subjects with tumor reduction
to obtain the proportion of subjects with tumor reduction of at least 10%
Measured: after 10-28 days of single agent lenvatinib
Comparison of the clinical response of lenvatinib in RET negative versus RET positive, ER positive breast cancers
To compare clinical response of lenvatinib in RET negative versus RET positive, ER positive breast cancers
Measured: after 10-28 days of single agent lenvatinib
Comparison in the overall average changes in biological effects of lenvatinib between RET negative and RET positive, ER positive breast cancers.
: Comparison of the number of patients with Ki67 changes, histological response, apoptosis, RET and downstream targets such as AKT and ERK, between RET negative versus RET positive, ER positive breast cancers.
Measured: after 10-28 days of single agent lenvatinib
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start28 Mar 2017
- Primary completion28 Mar 2021 (estimated)
- Study completion28 Mar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A Phase II window-of-opportunity study of single agent lenvatinib in estrogen receptor positive early stage breast cancer
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Co., Ltd., Tan Tock Seng Hospital
- Responsible party
- Sponsor
- Investigators
- Soo Chin Lee, Principal investigator, National University Hospital, SingaporeChing Wan Chan, Principal investigator, National University of SingaporeErn Yu Tan, Principal investigator, Tan Tock Seng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03168074
- Sponsor's protocol ID
- BR02/07/16
- Status last verified
- Feb 2017
- First submitted
- 26 Mar 2017
- Last updated
- 16 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Boulay A, Breuleux M, Stephan C, Fux C, Brisken C, Fiche M, Wartmann M, Stumm M, Lane HA, Hynes NE. The Ret receptor tyrosine kinase pathway functionally interacts with the ERalpha pathway in breast cancer. Cancer Res. 2008 May 15;68(10):3743-51. doi: 10.1158/0008-5472.CAN-07-5100.
PubMed 18483257Plaza-Menacho I, Morandi A, Robertson D, Pancholi S, Drury S, Dowsett M, Martin LA, Isacke CM. Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance. Oncogene. 2010 Aug 19;29(33):4648-57. doi: 10.1038/onc.2010.209. Epub 2010 Jun 7.
PubMed 20531297Morandi A, Martin LA, Gao Q, Pancholi S, Mackay A, Robertson D, Zvelebil M, Dowsett M, Plaza-Menacho I, Isacke CM. GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. Cancer Res. 2013 Jun 15;73(12):3783-95. doi: 10.1158/0008-5472.CAN-12-4265. Epub 2013 May 6.
PubMed 23650283
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Window-of-opportunity Study of Single Agent Lenvatinib in Estrogen Receptor Positive Early Stage Breast Cancer
- ClinicalTrials.gov ID
- NCT03168074
- Acronym / sponsor ID
- BR02/07/16
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- Eisai Co., Ltd., Tan Tock Seng Hospital
- Study start
- 28 Mar 2017 (actual)
- Primary completion
- 28 Mar 2021 (estimated)
- Study completion
- 28 Mar 2021 (estimated)
- First posted
- 30 May 2017 (actual)
- 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.
The Investigators hypothesize that single agent lenvatinib has biological activity in estrogen receptor positive breast cancer, and that the effects are more pronounced in patients with positive RET expression in the tumor.
Detailed description
Background and Rationale of Study:
- RET and Endocrine Resistance in Breast Cancer RET is an estrogen response gene, and preclinical studies have demonstrated cross talk between RET and ER. Significant interactions between RET and ERα pathways have been described, with increased response to estrogen stimulation observed in the presence of functional RET. RET is associated with resistance to tamoxifen and aromatase inhibitors, and increased RET expression has been demonstrated in hormone resistant cell lines and primary tumors.Combined anti-estrogen and anti-RET therapy in luminal breast cancer had a greater effect on cell growth than either therapy alone. The two classes of drugs have different mechanisms of action; a RET TKI reduced growth through induction of apoptosis, while anti-ERα reduced cell proliferation, forming the biologic basis for dual treatment.Dual therapy with tamoxifen and vandetinib, a RET inhibitor, resulted in greater reduction in tumor growth rate in MCF7 xenografts in mice.RET has been reported to be over-expressed in up to 75% of ER+ breast cancers (n=20), compared to only 10% of ER-negative breast cancers (n=10) in a small study. Recently, the investigators tested 94 archival breast cancer specimens from the National University Hospital, Singapore and found RET over-expression (2-3+) to be present in 59% of ER negative breast cancers (n=39) and 62% of ER positive breast cancers (n=55)
There is limited clinical experience in combining RET inhibitors with endocrine therapy in breast cancer, with only one reported study using vandetanib. In this study, 127 post-menopausal metastatic breast cancer patients with hormone receptor-positive, bone-predominant disease, were randomized to fulvestrant alone versus fulvestrant combined with vandetanib. No differences in clinical benefit rate, progression-free survival, or overall survival, were noted between the two treatment groups. Vandetanib, however, is a less potent inhibitor of RET than lenvatinib. Lenvatinib has been granted orphan drug designation for thyroid cancer by the United States Food and Drug Administration in 2013, but is not being actively developed in breast cancer.
The investigators tested 9 ER+ breast cancer cell lines for RET expression using Western blot, and identified 4 with high expression (BT474, MB361, HCC1419, UACC812), 2 with normal expression (MCF7, CAMA1), and 3 with low expression (T47D, ZR-75-1, BT483). To evaluate the effects of combining lenvatinib with endocrine therapy in ER+ breast cancer cell lines with different RET expression, the investigators performed experiments using 6 cell lines, including 2 with high RET expression (BT474, MB361), 2 with normal RET expression (MCF7, CAMA1), and 2 with low RET expression (T47D, ZR-75-1). IC50 to tamoxifen and lenvatinib alone was established for each cell line, followed by combination therapy at 3 different doses for each drug. Cell apoptosis and proliferation was measured using caspase 3/7 and MTT assays respectively. Preliminary experiments showed lenvatinib to have activity in ER positive breast cancer cell lines, regardless of levels of RET expression. Lenvatinib was at least additive with tamoxifen in all 6 ER positive breast cancer cell lines tested, with the combination resulting in ≥50% cell kill compared to single agent tamoxifen in BT474, CAMA1, and T47D cell lines. These pre-clinical observations suggest the potential role of lenvatinib in combination with endocrine therapy in the treatment of ER positive breast cancers.
Cells were seeded on 96-well plates and after 24 hours, the cells were treated with tamoxifen and lenvatinib simultaneously at different doses (tamoxifen at 0, 1, or 5µM, lenvatinib at 0, 5, 10 µM) and incubated for 72 hours. Cell viability was assessed using CCK-8 assay.
- Preliminary observation of clinical activity of single agent lenvatinib in hormone receptor positive breast cancer
The investigators previously hypothesized that combining a RET inhibitor such as lenvatinib with endocrine therapy may potentiate anti-tumor effects in hormone receptor positive breast cancers. The investigators have recently initiated a study of lenvatinib + letrozole as neoadjuvant therapy in hormone receptor positive breast cancer patients. Eligible patients were treated with two weeks of single agent lenvatinib, followed by 12 weeks of lenvatinib + letrozole. Two patients have been enrolled and the investigators observed tumor reduction of 10-15% on ultrasound after 2 weeks of single agent lenvatinib. To confirm these interesting observations, the investigators intend to treat a larger cohort of patients with newly diagnosed early stage breast cancer who are awaiting definitive breast cancer surgery with approximately 2 weeks of single agent lenvatinib using a window-of-opportunity design, and evaluate tumor response on ultrasound and histological changes from pre- and post-treatment tumor biopsies. This design will allow the investigators to expand the target population for rapid enrollment to achieve a quick signal on biological activity of lenvatinib in human breast cancers in vivo.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A Phase II window-of-opportunity study of single agent lenvatinib in estrogen receptor positive early stage breast cancer
| Arm | Type | Receives |
|---|---|---|
| lenvatinib | Experimental | Drug: lenvatinibEligible patients will be treated with approximately 2 weeks of single agent lenvatinib (range 10-28 days, depending on the date of breast cancer surgery; last dose of lenvatinib to be administered no later than 48 hours before surgery in patients who are planned to receive ≤14 days lenvatinib, and no later than 120 hours before surgery in patients who are planned to receive 15-28 days lenvatinib). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients must fulfill ALL the following inclusion criteria
- Female ≥18 years
- Histological or cytological diagnosis of breast carcinoma
- No prior treatment for current breast carcinoma
- Scheduled for upfront definitive breast cancer surgery (breast conserving surgery or mastectomy with or without sentinel lymph node biopsy or axillary lymph node clearance)
Key exclusion criteria (12 listed)
- Scheduled for neoadjuvant systemic therapy
- Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- Treatment within the last 28 days with any investigational drug.
- Major surgery within 28 days of study drug administration.
- Pregnancy.
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 |
|---|---|---|
| lenvatinibEligible patients will be treated with approximately 2 weeks of single agent lenvatinib (range 10-28 days, depending on the date of breast cancer surgery; last dose of lenvatinib to be administered no later than 48 hours before surgery in patients who are planned to receive ≤14 days lenvatinib, and no later than 120 hours before surgery in patients who are planned to receive 15-28 days lenvatinib).Tissue sections from the pre-treatment and post-treatment tumor will be collected for biomarker analysis. Pre- and post-treatment ultrasound will be used to document the size of the target lesions. | Drug | lenvatinib |
Primary outcome
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
Time frame: after 10-28 days of single agent lenvatinib
To evaluate Ki67 changes. The Ki-67 protein is a cellular marker for proliferation. It is strictly associated with cell proliferation. Ki67 has been shown to be a surrogate marker of biological activity and treatment response in estrogen receptor positive breast cancer treated with endocrine therapy.
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
Time frame: after 10-28 days of single agent lenvatinib
To evaluate histological response such as the improvement in the appearance of microscopic tissue specimens after treatment with lenvatinib. The improved appearance of biopsy specimens after treatment often suggests the patient's prognosis will improve as well.
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
Time frame: after 10-28 days of single agent lenvatinib
To evaluate apoptosis. Apoptosis is the death of cells which occurs as a normal and controlled part of an organism's growth or development. The presence of apoptosis indicates anti-cancer effects.
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
Time frame: after 10-28 days of single agent lenvatinib
To evaluate RET. RET is an estrogen response gene. RET is associated with resistance to tamoxifen and aromatase inhibitors, and increased RET expression has been demonstrated in hormone resistant cell lines and primary tumors.
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
Time frame: after 10-28 days of single agent lenvatinib
To evaluate downstream targets such as AKT. AKT /protein kinase B (PKB) is a cardinal node in diverse signaling cascades important in both normal cellular physiology and various disease states. AKT signaling regulates cell proliferation and survival, cell growth (size), glucose metabolism, cell motility and angiogenesis. Aberrant regulation of these processes results in cellular perturbations considered hallmarks of cancer, and numerous studies testify to the frequent hyperactivation of AKT signaling in many human cancer.
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design
Time frame: after 10-28 days of single agent lenvatinib
To evaluate downstream targets such as ERK. ERK is Extracellular signal-regulated kinase. Deregulation of ERK signalling pathway is linked to many other aspects of the tumour phenotype.
4 secondary outcomes
Changes in the primary tumor dimensions
Time frame: after 10-28 days of single agent lenvatinib
The proportion of subjects with tumor reduction
Time frame: after 10-28 days of single agent lenvatinib
Comparison of the clinical response of lenvatinib in RET negative versus RET positive, ER positive breast cancers
Time frame: after 10-28 days of single agent lenvatinib
Comparison in the overall average changes in biological effects of lenvatinib between RET negative and RET positive, ER positive breast cancers.
Time frame: after 10-28 days of single agent lenvatinib
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2017.
- Background: PubMed 18483257Boulay A, Breuleux M, Stephan C, Fux C, Brisken C, Fiche M, Wartmann M, Stumm M, Lane HA, Hynes NE. The Ret receptor tyrosine kinase pathway functionally interacts with the ERalpha pathway in breast cancer. Cancer Res. 2008 May 15;68(10):3743-51. doi: 10.1158/0008-5472.CAN-07-5100.
- Background: PubMed 20531297Plaza-Menacho I, Morandi A, Robertson D, Pancholi S, Drury S, Dowsett M, Martin LA, Isacke CM. Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance. Oncogene. 2010 Aug 19;29(33):4648-57. doi: 10.1038/onc.2010.209. Epub 2010 Jun 7.
- Background: PubMed 23650283Morandi A, Martin LA, Gao Q, Pancholi S, Mackay A, Robertson D, Zvelebil M, Dowsett M, Plaza-Menacho I, Isacke CM. GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. Cancer Res. 2013 Jun 15;73(12):3783-95. doi: 10.1158/0008-5472.CAN-12-4265. Epub 2013 May 6.
- Individual participant dataSharing planned: No
Related trials for Breast Cancer
Not yet recruiting
Effect of a Health Belief Model Based Digital Nudge Intervention on Breast Cancer Screening
Breast Cancer Screening, Breast Cancer Awareness
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Not yet recruitingPhase 2
Low-Dose Apatinib Plus Chemotherapy in ADC-Pretreated HER2-Positive and HER2-Low Advanced Breast Cancer
Breast Neoplasms, Advanced Breast Cancer
RecruitingPhase 3
ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients With Triple-Negative Breast Cancer
Breast Neoplasms
Active, not recruitingPhase 2
Phase II Study of Dato-DXd in Triple-negative Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases
Breast Cancer Stage IV
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.
Soo Chin Lee principal investigator
National University Hospital, Singapore
Ching Wan Chan principal investigator
National University of Singapore
Ern Yu Tan principal investigator
Tan Tock Seng Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lenvatinib in people with Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
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 20 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 16 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Soo Chin Lee ((65) 6779 5555, soo_chin_lee@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design (time frame: after 10-28 days of single agent lenvatinib). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03168074, which also lists 3 linked publications.
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 16 Jun 2017.