Clinical trial NCT02936206: Examination of Breast Cancer Cells of Pre-menopausal and Post-menopausal Women Before and After Exposure to Tamoxifen or Fulvestrant.
Official title: Comparison in the Change of Proliferation Index Between Fulvestrant and Tamoxifen in Cyclin D1 +, Estrogen Receptor + Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: proliferation Index
Tamoxifen
Fulvestrant
cyclinD1
Breast cancer
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2016-10-18
Enrollment: 2
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to microscopically examine breast cancer cells of pre-menopausal and post-menopausal women before and after exposure to one of the two commonly used breast cancer drugs, tamoxifen or fulvestrant.

Detailed description: The researchers hypothesize that the cyclinD1-interactome can be used to orient the use of fulvestrant in premenopausal and postmenopausal women. To test this hypothesis, the researchers propose a pre-surgical randomized clinical trial of tamoxifen vs fulvestrant in the window between breast cancer diagnosis on core biopsy and definitive surgery. Women with ER/cyclinD1 positive tumors will be eligible. Response to tamoxifen or fulvestrant will be evaluated using standard proliferation index as well as gene expression signatures obtained in pre-clinical models of tamoxifen resistance and sensitivity to fulvestrant. In addition, the researchers propose to use cutting edge new technology allowing ex-vivo expansion of primary culture from only a few cancer cells obtained by fine needle biopsy. The researchers propose to compare the response of these primary cells to patient response. If successful, the impact of this work can support the expansion of use of fulvestrant to not only postmenopausal women but premenopausal women as well. In addition, it may serve as a proof of principle to maximize the use of biopsy material to predict treatment response

Eligibility criteria: Inclusion Criteria:

* Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the study treatment regimen and follow-up, must be obtained and documented according to the local regulatory requirements
* Adult women greater than 18 years old
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
* New diagnosis of invasive cyclin D1 +, ER+, PR +/-, Her2- breast cancer

  * Cyclin D1 positive as defined as a total immunohistochemical score of 5 or greater
  * Hormone receptor positive as defined as ≥ 10% positive stained cells
  * HER2-normal (IHC score 0-1 or FISH negative \[in-situ hybridization (ISH) ratio \<= 2.0 status\])
* Tumor size at least 5 mm with planned primary surgery at Mount Sinai
* A negative urine dipstick pregnancy test

Exclusion Criteria:

* Estrogen receptor negative invasive breast carcinoma as defined as less than 10% stained cells
* Prior antiestrogen therapy
* Tumor size less than 5 mm
* Prior diagnosis of thrombosis or known hypercoagulable state
* Known history of bleeding diathesis
* Known liver disease
* Prior treatment with neoadjuvant therapy
* Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema).
* Current severe or uncontrolled systemic disease
* Pregnancy or lactation period. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices) during study treatment.
* Prior malignancy (including invasive or ductal in-situ breast cancer) within 5 years prior to randomization, except curatively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix.

Primary outcomes:
measure: Change in Ki67 Cell Percentage
timeFrame: baseline and 2 weeks
Secondary outcomes:
measure: Change in Estrogen Receptor Level
timeFrame: baseline and 2 weeks
measure: Change in Progesterone Receptor Level
timeFrame: baseline and 2 weeks
measure: Incidence of Tamoxifen-resistance Gene Expression
timeFrame: 2 weeks
measure: Incidence of Fulvestrant-sensitivity Gene Expression
timeFrame: 2 weeks
measure: Drug Dose Level
timeFrame: 2 weeks
measure: Percentage of Cells Staining Positive Within the Breast Tumor
timeFrame: 2 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Mount Sinai St. Luke's
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Amy Tiersten, MD
role: PRINCIPAL_INVESTIGATOR
References: