Phase II Study of Single Agent Lenvatinib

NCT03168074 | Unknown Phase 2

• 1 other identifier: BR02/07/16
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (4)

• Changes in the primary tumor dimensions

  after 10-28 days of single agent lenvatinib

• The proportion of subjects with tumor reduction

  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

  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.

  after 10-28 days of single agent lenvatinib

Study Arms (1)

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).

Drug: lenvatinib

Interventions

lenvatinib DRUG

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.

lenvatinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Gender Eligibility Details: The study is designed for breast cancer patients. Male breast cancer is extremely rare and we do not intend to include this rare population.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Eisai Co., Ltd.: collaborator
• Tan Tock Seng Hospital: collaborator

Study Sites (1)

Nationa University Hospital

Singapore, Singapore

RECRUITING

Related Publications (3)

• 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.

  PMID: 18483257 BACKGROUND

• 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.

  PMID: 20531297 BACKGROUND

• 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.

  PMID: 23650283 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Soo Chin Lee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

• Ching Wan Chan

  National University of Singapore

  PRINCIPAL INVESTIGATOR

• Ern Yu Tan

  Tan Tock Seng Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soo Chin Lee

CONTACT

(65) 6779 5555; soo_chin_lee@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Phase II window-of-opportunity study of single agent lenvatinib in estrogen receptor positive early stage breast cancer

Study Record Dates

• First Submitted: March 26, 2017
• First Posted: May 30, 2017
• Study Start: March 28, 2017
• Primary Completion: March 28, 2021
• Study Completion: March 28, 2021
• Last Updated: June 16, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)