search
Back to results

Examination of Breast Cancer Cells of Pre-menopausal and Post-menopausal Women Before and After Exposure to Tamoxifen or Fulvestrant.

Primary Purpose

Breast Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fulvestrant
Tamoxifen
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Breast Cancer focused on measuring proliferation Index, Tamoxifen, Fulvestrant, cyclinD1, Breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Mount Sinai West
  • Mount Sinai St. Luke's
  • Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Fulvestrant

Tamoxifen

Arm Description

750 mg injection in 3 divided doses

20mg orally

Outcomes

Primary Outcome Measures

Change in Ki67 Cell Percentage
The change in proliferation index as measured by the percentage of cells staining for Ki67 at 2 weeks as compared on baseline.

Secondary Outcome Measures

Change in Estrogen Receptor Level
The change in estrogen receptor level at 2 weeks as compared to baseline.
Change in Progesterone Receptor Level
The change in progesterone receptor level at 2 weeks as compared to baseline.
Incidence of Tamoxifen-resistance Gene Expression
Number of tamoxifen-resistance gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
Incidence of Fulvestrant-sensitivity Gene Expression
Number of fulvestrant-sensitivity gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
Drug Dose Level
For samples that are available for culture in vivo, proliferation assay to test whether the cells derived from individual patients respond the same as the tumor in vivo in the same patient.
Percentage of Cells Staining Positive Within the Breast Tumor
Differential treatment effect for pre and post menopausal subjects assessed by the mean change in levels (expressed as a percentage of cells staining positive within the breast tumor) of ER (and PR) between pre-treatment and post-treatment stratified by menopausal status.

Full Information

First Posted
October 14, 2016
Last Updated
April 27, 2021
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
AstraZeneca
search

1. Study Identification

Unique Protocol Identification Number
NCT02936206
Brief Title
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

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
low accrual rate
Study Start Date
October 2016 (undefined)
Primary Completion Date
May 1, 2020 (Actual)
Study Completion Date
May 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
proliferation Index, Tamoxifen, Fulvestrant, cyclinD1, Breast cancer

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fulvestrant
Arm Type
Experimental
Arm Description
750 mg injection in 3 divided doses
Arm Title
Tamoxifen
Arm Type
Active Comparator
Arm Description
20mg orally
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
Faslodex
Intervention Description
fulvestrant 750 mg (three 5 ml injections slowly over 1-2 mn per injection in the buttocks) on day 1 only
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Other Intervention Name(s)
Nolvadex
Intervention Description
14 days of treatment with tamoxifen 20mg orally each day
Primary Outcome Measure Information:
Title
Change in Ki67 Cell Percentage
Description
The change in proliferation index as measured by the percentage of cells staining for Ki67 at 2 weeks as compared on baseline.
Time Frame
baseline and 2 weeks
Secondary Outcome Measure Information:
Title
Change in Estrogen Receptor Level
Description
The change in estrogen receptor level at 2 weeks as compared to baseline.
Time Frame
baseline and 2 weeks
Title
Change in Progesterone Receptor Level
Description
The change in progesterone receptor level at 2 weeks as compared to baseline.
Time Frame
baseline and 2 weeks
Title
Incidence of Tamoxifen-resistance Gene Expression
Description
Number of tamoxifen-resistance gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
Time Frame
2 weeks
Title
Incidence of Fulvestrant-sensitivity Gene Expression
Description
Number of fulvestrant-sensitivity gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
Time Frame
2 weeks
Title
Drug Dose Level
Description
For samples that are available for culture in vivo, proliferation assay to test whether the cells derived from individual patients respond the same as the tumor in vivo in the same patient.
Time Frame
2 weeks
Title
Percentage of Cells Staining Positive Within the Breast Tumor
Description
Differential treatment effect for pre and post menopausal subjects assessed by the mean change in levels (expressed as a percentage of cells staining positive within the breast tumor) of ER (and PR) between pre-treatment and post-treatment stratified by menopausal status.
Time Frame
2 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Tiersten, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai West
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Mount Sinai St. Luke's
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Examination of Breast Cancer Cells of Pre-menopausal and Post-menopausal Women Before and After Exposure to Tamoxifen or Fulvestrant.

We'll reach out to this number within 24 hrs