Breast Cancer Clinical Trial
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.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | March 28, 2021 |
Est. primary completion date | March 28, 2021 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years to 99 Years |
Eligibility |
Inclusion Criteria: 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%) - 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 Exclusion Criteria: 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. - 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. |
Country | Name | City | State |
---|---|---|---|
Singapore | Nationa University Hospital | Singapore |
Lead Sponsor | Collaborator |
---|---|
National University Hospital, Singapore | Eisai Co., Ltd., Tan Tock Seng Hospital |
Singapore,
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. — View Citation
Morandi 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. — View Citation
Plaza-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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | after 10-28 days of single agent lenvatinib | |
Primary | 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. | after 10-28 days of single agent lenvatinib | |
Primary | 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. | after 10-28 days of single agent lenvatinib | |
Primary | 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. | after 10-28 days of single agent lenvatinib | |
Primary | 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. | after 10-28 days of single agent lenvatinib | |
Primary | 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. | after 10-28 days of single agent lenvatinib | |
Secondary | Changes in the primary tumor dimensions | to obtain the percentage change in primary breast tumor dimension measured by ultrasound | after 10-28 days of single agent lenvatinib | |
Secondary | The proportion of subjects with tumor reduction | to obtain the proportion of subjects with tumor reduction of at least 10% | after 10-28 days of single agent lenvatinib | |
Secondary | 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 | after 10-28 days of single agent lenvatinib | |
Secondary | 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. | after 10-28 days of single agent lenvatinib |
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