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

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ClinicalTrials.gov Identifier: NCT02936206
Recruitment Status : Recruiting
First Posted : October 18, 2016
Last Update Posted : November 6, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Amy Tiersten, Icahn School of Medicine at Mount Sinai

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Fulvestrant Drug: Tamoxifen Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Comparison in the Change of Proliferation Index Between Fulvestrant and Tamoxifen in Cyclin D1 +, Estrogen Receptor + Breast Cancer
Study Start Date : October 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Fulvestrant
750 mg injection in 3 divided doses
Drug: Fulvestrant
fulvestrant 750 mg (three 5 ml injections slowly over 1-2 mn per injection in the buttocks) on day 1 only
Other Name: Faslodex

Active Comparator: Tamoxifen
20mg orally
Drug: Tamoxifen
14 days of treatment with tamoxifen 20mg orally each day
Other Name: Nolvadex




Primary Outcome Measures :
  1. Change in Ki67 cell percentage [ Time Frame: baseline and 2 weeks ]
    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 :
  1. Change in estrogen receptor level [ Time Frame: baseline and 2 weeks ]
    The change in estrogen receptor level at 2 weeks as compared to baseline.

  2. Change in progesterone receptor level [ Time Frame: baseline and 2 weeks ]
    The change in progesterone receptor level at 2 weeks as compared to baseline.

  3. Incidence of tamoxifen-resistance gene expression [ Time Frame: 2 weeks ]
    Number of tamoxifen-resistance gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.

  4. Incidence of fulvestrant-sensitivity gene expression [ Time Frame: 2 weeks ]
    Number of fulvestrant-sensitivity gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.

  5. drug dose level [ Time Frame: 2 weeks ]
    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.

  6. Percentage of cells staining positive within the breast tumor [ Time Frame: 2 weeks ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

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): NCT02936206


Contacts
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Contact: Neha Kumarley 212-824-7659 neha.kumarley@mssm.edu

Locations
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United States, New York
Mount Sinai West Recruiting
New York, New York, United States, 10019
Contact: Takhir Mirzoyev    212-523-7289    Takhir.mirzoyev@mountsinai.org   
Principal Investigator: Anupama Goel, MD         
Mount Sinai St. Luke's Recruiting
New York, New York, United States, 10025
Contact: Audra Caine    212-523-6828    Audra.caine@mountsinai.org   
Principal Investigator: Aye Moe Thu Ma, MD         
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: Amy Tiersten, MD         
Sub-Investigator: Krystal Cascetta, MD         
Sub-Investigator: Paul H Schmidt, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
AstraZeneca
Investigators
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Principal Investigator: Amy Tiersten, MD Icahn School of Medicine at Mount Sinai

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Responsible Party: Amy Tiersten, Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT02936206     History of Changes
Other Study ID Numbers: GCO 16-1470
First Posted: October 18, 2016    Key Record Dates
Last Update Posted: November 6, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Amy Tiersten, Icahn School of Medicine at Mount Sinai:
proliferation Index
Tamoxifen
Fulvestrant
cyclinD1
Breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Fulvestrant
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists