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Phase II Study of Single Agent Lenvatinib

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ClinicalTrials.gov Identifier: NCT03168074
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : June 16, 2017
Sponsor:
Collaborators:
Eisai Co., Ltd.
Tan Tock Seng Hospital
Information provided by (Responsible Party):
National University Hospital, Singapore

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: lenvatinib Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: A Phase II Window-of-opportunity Study of Single Agent Lenvatinib in Estrogen Receptor Positive Early Stage Breast Cancer
Actual Study Start Date : March 28, 2017
Estimated Primary Completion Date : March 28, 2021
Estimated Study Completion Date : March 28, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Lenvatinib

Arm Intervention/treatment
Experimental: lenvatinib
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
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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. Changes in the primary tumor dimensions [ Time Frame: after 10-28 days of single agent lenvatinib ]
    to obtain the percentage change in primary breast tumor dimension measured by ultrasound

  2. The proportion of subjects with tumor reduction [ Time Frame: after 10-28 days of single agent lenvatinib ]
    to obtain the proportion of subjects with tumor reduction of at least 10%

  3. 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 ]
    To compare clinical response of lenvatinib in RET negative versus RET positive, ER positive breast cancers

  4. 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 ]
    : 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.



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   The study is designed for breast cancer patients. Male breast cancer is extremely rare and we do not intend to include this rare population.
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03168074


Contacts
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Contact: Soo Chin Lee (65) 6779 5555 soo_chin_lee@nuhs.edu.sg

Locations
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Singapore
Nationa University Hospital Recruiting
Singapore, Singapore
Contact: Soo Chin Lee, MBBS, MRCP    +65 6779 5555    Soo_Chin_Lee@nuhs.edu.sg   
Principal Investigator: Soo Chin Lee, MBBS, MRCP         
Sponsors and Collaborators
National University Hospital, Singapore
Eisai Co., Ltd.
Tan Tock Seng Hospital
Investigators
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Principal Investigator: Soo Chin Lee National University Hospital, Singapore
Principal Investigator: Ching Wan Chan National University Cancer Institute, Singapore
Principal Investigator: Ern Yu Tan Tan Tock Seng Hospital

Publications:
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Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT03168074     History of Changes
Other Study ID Numbers: BR02/07/16
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: June 16, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action