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

Breast Cancer Clinical Trial

Official title:

Comparison in the Change of Proliferation Index Between Fulvestrant and Tamoxifen in Cyclin D1 +, Estrogen Receptor + Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02936206
• Other study ID #: GCO 16-1470
• Status: Terminated
• Phase: Phase 1
• Start date: October 2016
• Est. completion date: May 1, 2020

Study information

• Verified date: April 2021
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: May 1, 2020
• Est. primary completion date: May 1, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Fulvestrant
fulvestrant 750 mg (three 5 ml injections slowly over 1-2 mn per injection in the buttocks) on day 1 only
• Tamoxifen
14 days of treatment with tamoxifen 20mg orally each day

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Mount Sinai St. Luke's	New York	New York
United States	Mount Sinai West	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline and 2 weeks
Secondary	Change in Estrogen Receptor Level	The change in estrogen receptor level at 2 weeks as compared to baseline.	baseline and 2 weeks
Secondary	Change in Progesterone Receptor Level	The change in progesterone receptor level at 2 weeks as compared to baseline.	baseline and 2 weeks
Secondary	Incidence of Tamoxifen-resistance Gene Expression	Number of tamoxifen-resistance gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.	2 weeks
Secondary	Incidence of Fulvestrant-sensitivity Gene Expression	Number of fulvestrant-sensitivity gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.	2 weeks
Secondary	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.	2 weeks
Secondary	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.	2 weeks