Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients

NCT ID: NCT01027416

Last Updated: 2017-12-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-12-14

Study Completion Date

2015-12-31

Brief Summary

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This study will help to understand the interaction between estrogen receptor-alpha (ER alpha) and tumor suppressor protein p53 as well as impact on patient tumor gene expression in response to the hormonal therapy Tamoxifen. This information may eventually help select the appropriate therapy for future patients with similar cancer.

Detailed Description

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Women with abnormal mammogram or suspicious masses will undergo diagnostic core biopsies which will be analyzed for ER/PR and HER2Neu expression. For patients that are ER positive, p53 staining will be done.

Women presenting tumors with an Allred score of 3 or greater status will be approached to participate.

Women will be randomized to either standard of care surgical therapy or a 4 week intervention of Tamoxifen 20mg daily for 4 weeks prior to surgery. During the intervention, blood draws will be done to measure levels of tamoxifen metabolites in the blood and test for polymorphisms that may decrease levels of active metabolites.

Women will undergo two blood draws for PK/PD and one for pharmacogenomics. Tissue microarray (TMA) will be generated from resected tumors for immunohistochemistry (IHC) and proximity ligation assay (PLA) for measuring ER alpha-p53 interaction.

Tumor tissue will be used for analyzing tamoxifen metabolites and estradiol levels. RNA and proteins from the tumors will be used for analyzing gene expression.

Conditions

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Breast Cancer

Keywords

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ER positive Tamoxifen

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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No Intervention

Group Type NO_INTERVENTION

No interventions assigned to this group

Tamoxifen

Tamoxifen 20 mg orally 1x/day for 4 weeks

Group Type ACTIVE_COMPARATOR

Tamoxifen

Intervention Type DRUG

Drug: Tamoxifen 20 mg orally 1x/day for 4 weeks

Interventions

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Tamoxifen

Drug: Tamoxifen 20 mg orally 1x/day for 4 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. The patient must consent to be in the study and must have signed an approved consent form conforming to institutional guidelines
2. The patient must be 18 years or older.
3. Core biopsy should definitively demonstrate invasive carcinoma.
4. Invasive carcinoma should be ER-apha receptor positive
5. The tumor should be approximately at least 1 cm, to account for variability in imaging and imaging occult disease (physical exam, mammography, ultrasound). We recognize that from time to time because of this variation, there might not be enough tissue available for analysis after surgical excision but this will allow the greatest opportunity to capture as many eligible patients as possible.
6. Patients in whom surgical excision of the tumor is part of standard of care management
7. ECOG score of 0 or 1
8. Negative serum or urine beta-hCG pregnancy test at screening for patients of child-bearing potential (this is routinely done if the patient is premenopausal and having surgery)
9. Consent to participate in DBBR (RPCI only)

Exclusion Criteria

1. Male patients are not eligible for this study
2. Female patients with inoperable tumors or women with stage 4 disease diagnosed on CT, PET, PET/CT or bone scan.
3. Patients with diagnosis by FNA cytology only
4. Pregnant or lactating women
5. Prior therapy for breast cancer, including irradiation, chemo- immuno- and/or hormonal therapy
6. Patients receiving any hormonal therapy, e.g. ovarian hormonal replacement therapy, infertility medications etc., are not eligible
7. Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from being subjected to surgical excision
8. Psychiatric or addictive disorders that would preclude obtaining informed consent
9. Patients known or suspected to have hypercoagulable syndrome or with history of venous or arterial thrombosis, stroke, TIA, or pulmonary embolism
10. Women with non-invasive disease or microinvasion are not eligible.
11. Women undergoing neoadjuvant chemotherapy are not eligible
12. women currently on tamoxifen and raloxifene for prevention are not eligible
13. Patients shall not receive any herbal/alternative therapies such as flaxseed or soy products or black cohosh.
14. Patients with a known mutation in p53 (Li Fraumeni Syndrome)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gokul Das, PhD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

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University of Chicago

Chicago, Illinois, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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R21CA137635-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RPCI I 110907

Identifier Type: -

Identifier Source: org_study_id

NCT01658566

Identifier Type: -

Identifier Source: nct_alias