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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 : Terminated (low accrual rate)
First Posted : October 18, 2016
Results First Posted : May 19, 2021
Last Update Posted : May 19, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Amy Tiersten, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE October 14, 2016
First Posted Date  ICMJE October 18, 2016
Results First Submitted Date  ICMJE April 27, 2021
Results First Posted Date  ICMJE May 19, 2021
Last Update Posted Date May 19, 2021
Study Start Date  ICMJE October 2016
Actual Primary Completion Date May 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
Change in Ki67 cell percentage [ Time Frame: baseline and 22 days ]
The change in proliferation index as measured by the percentage of cells staining for Ki67 at 22 days as compared on baseline.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2021)
  • Change in Estrogen Receptor Level [ Time Frame: baseline and 2 weeks ]
    The change in estrogen receptor level at 2 weeks as compared to baseline.
  • Change in Progesterone Receptor Level [ Time Frame: baseline and 2 weeks ]
    The change in progesterone receptor level at 2 weeks as compared to baseline.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
  • Change in estrogen receptor level [ Time Frame: baseline and 22 days ]
    The change in estrogen receptor level at 22 days as compared to baseline.
  • Change in progesterone receptor level [ Time Frame: baseline and 22 days ]
    The change in progesterone receptor level at 22 days as compared to baseline.
  • Incidence of tamoxifen-resistance gene expression [ Time Frame: 22 days ]
    Number of tamoxifen-resistance gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
  • Incidence of fulvestrant-sensitivity gene expression [ Time Frame: 22 days ]
    Number of fulvestrant-sensitivity gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
  • drug dose level [ Time Frame: 22 days ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Examination of Breast Cancer Cells of Pre-menopausal and Post-menopausal Women Before and After Exposure to Tamoxifen or Fulvestrant.
Official Title  ICMJE Comparison in the Change of Proliferation Index Between Fulvestrant and Tamoxifen in Cyclin D1 +, Estrogen Receptor + Breast Cancer
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
  • Drug: Tamoxifen
    14 days of treatment with tamoxifen 20mg orally each day
    Other Name: Nolvadex
Study Arms  ICMJE
  • Experimental: Fulvestrant
    750 mg injection in 3 divided doses
    Intervention: Drug: Fulvestrant
  • Active Comparator: Tamoxifen
    20mg orally
    Intervention: Drug: Tamoxifen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 27, 2021)
2
Original Estimated Enrollment  ICMJE
 (submitted: October 14, 2016)
64
Actual Study Completion Date  ICMJE May 1, 2020
Actual Primary Completion Date May 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02936206
Other Study ID Numbers  ICMJE GCO 16-1470
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amy Tiersten, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Amy Tiersten, MD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP