Low-Dose Tamoxifen Citrate in Reducing Breast Cancer Risk in Radiation-Induced Cancer Survivors

NCT ID: NCT01196936

Last Updated: 2026-01-05

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-30

Study Completion Date

2028-12-11

Brief Summary

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Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells

This phase IIb trial studies how well low-dose tamoxifen citrate works in reducing breast cancer risk in radiation-induced cancer survivors.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the impact of a two-year course of low-dose tamoxifen (tamoxifen citrate) administered at 5 mg per day on surrogate endpoint biomarkers of breast cancer (BC) risk, including: mammographic breast density (MBD), an established radiographic biomarker of BC risk; cytomorphology and proliferative index, tissue biomarkers closely linked to BC risk; and sex steroid hormones and insulin growth factors, circulating biomarkers of BC risk.

II. To establish safety and tolerability of this low-dose tamoxifen regimen, assessing both objective measures (lipid profiles, clotting factors and bone metabolism markers) and patient-reported outcomes.

III. To examine the modifying effect of demographic, clinical, and molecular characteristics on the risk: benefit ratio from this two-year low dose tamoxifen intervention.

IV. To explore the relationship between this low-dose tamoxifen regimen and clinical measures of efficacy (new breast cancer and ductal carcinoma in situ \[DCIS\] diagnoses) and toxicity (thromboembolic events, reports of hot flashes and gynecological symptoms, liver function abnormalities, and other cancer diagnoses).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive tamoxifen citrate orally (PO) once daily for 24 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO once daily for 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 10 years.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Arm I (tamoxifen citrate)

Patients receive tamoxifen citrate PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Tamoxifen Citrate

Intervention Type DRUG

5 mg PO Daily

Digital mammography

Intervention Type PROCEDURE

Correlative studies

immunohistochemistry staining method

Intervention Type OTHER

Correlative Studies

pharmacological study

Intervention Type OTHER

Correlative Studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative Studies

protein expression analysis

Intervention Type GENETIC

correlative studies

pharmacogenomic studies

Intervention Type OTHER

correlative studies

questionnaire administration

Intervention Type OTHER

Ancillary studies

Fine needle aspiration

Intervention Type PROCEDURE

Quality of Life Assessment

Intervention Type OTHER

Ancillary Studies

Arm II (placebo)

Patients receive placebo PO QD for 24 months in the absence of disease progression or unacceptable toxicity.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

1 tablet daily

Digital mammography

Intervention Type PROCEDURE

Correlative studies

immunohistochemistry staining method

Intervention Type OTHER

Correlative Studies

pharmacological study

Intervention Type OTHER

Correlative Studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative Studies

protein expression analysis

Intervention Type GENETIC

correlative studies

pharmacogenomic studies

Intervention Type OTHER

correlative studies

questionnaire administration

Intervention Type OTHER

Ancillary studies

Fine needle aspiration

Intervention Type PROCEDURE

Quality of Life Assessment

Intervention Type OTHER

Ancillary Studies

Interventions

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Tamoxifen Citrate

5 mg PO Daily

Intervention Type DRUG

Placebo

1 tablet daily

Intervention Type DRUG

Digital mammography

Correlative studies

Intervention Type PROCEDURE

immunohistochemistry staining method

Correlative Studies

Intervention Type OTHER

pharmacological study

Correlative Studies

Intervention Type OTHER

laboratory biomarker analysis

Correlative Studies

Intervention Type OTHER

protein expression analysis

correlative studies

Intervention Type GENETIC

pharmacogenomic studies

correlative studies

Intervention Type OTHER

questionnaire administration

Ancillary studies

Intervention Type OTHER

Fine needle aspiration

Intervention Type PROCEDURE

Quality of Life Assessment

Ancillary Studies

Intervention Type OTHER

Other Intervention Names

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Marketed under trade name Nolvadex as 10 mg and 20 mg tablets ICI 46,474 Correlative studies

Eligibility Criteria

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Inclusion Criteria

* Exposure to radiation therapy (RT) delivered to the chest, axilla, and/or supraclavicular areas at a cumulative dose of 12 Gy or more by age 40 years; in addition, patients who received total body irradiation by age 40 may be considered
* No evidence of active disease from their primary cancer for at least 2 continuous years prior to registration; the indication for RT is not specified but cannot be for primary breast cancer; common examples include, but are not limited to: lymphoma, leukemia, sarcoma, and Wilms tumor occurring in pediatric patients, and lymphoma, leukemia, and sarcoma occurring in young adults; primary cancer therapy must have been completed at least 6 months prior to registration
* Well-defined menopausal status falling into one of the following categories:

* Premenopausal, defined as age at registration 45 years old or younger with regular monthly period for at least 6 consecutive months prior to registration
* Postmenopausal, defined as continuous absence of menstruation for 12 months OR status-post bilateral oophorectomy OR follicle stimulating hormone (FSH) level in the postmenopausal range

Exclusion Criteria

* Subsequent malignant neoplasm (SMN) other than those listed below diagnosed within 2 years of study entry; patients with the listed indolent or pre-invasive neoplasms may be eligible if diagnosed within 2 years and all treatment was completed at least 6 months prior to registration:

* Non-melanoma cancers of the skin
* Thyroid cancer
* Cervical cancer confined to the cervix or cervical intraepithelial neoplasia (CIN)
* Ductal carcinoma in situ (DCIS) or breast intraepithelial neoplasia (IEN) (includes atypical hyperplasia and lobular carcinoma in situ \[LCIS\]), or
* Superficial or non-invasive transitional cell carcinoma of the bladder
* For women with a prior history of DCIS or breast IEN, only one breast could have been involved and all therapy must have been completed at least 6 months prior to registration; in addition women with a prior history of invasive breast cancer may also be eligible, as long as only one breast was involved, they were diagnosed at least 2 years prior to study entry, and therapy was completed at least 6 months prior to study entry
* Bilateral breast implants or status-post bilateral prophylactic mastectomy
* Evidence of malignant breast disease on any form of breast imaging; the study only requires annual mammography; however, annual breast magnetic resonance imaging (MRI) is considered standard of care in this patient population (per Children's Oncology Group \[COG\] or National Comprehensive Cancer Network \[NCCN\] follow-up guidelines), and breast ultrasound may be indicated if a palpable lesion is detected on screening clinical breast exam; abnormal imaging may require additional radiographs and/or breast biopsy; patients who are found to have benign breast disease with or without atypia may continue on study as long as there is no evidence of malignancy; if there is evidence of malignancy, and only one breast is involved, they may be reapproached 6 months after completion of therapy for consideration of the trial
* Baseline categorical mammographic density scored as BIRAD 1, or extremely fatty, in both breasts; if the patient has a prior history of IEN (DCIS, LCIS, or atypical hyperplasia), the contralateral breast must not have a mammographic density score of BIRAD 1; this determination will be made at the local site
* Current or recent use (within 6 months of registration or baseline mammogram, whichever is first) of any of the following: systemic hormone replacement therapy (includes oral or transdermal formulations); Vagifem and Estring, two formulations of locally applied vaginal estrogen associated with minimal systemic absorption, may be allowed; other estrogen-containing vaginal creams, while not an exclusion, should be avoided whenever possible; patients with a history of hormone modifying herbal supplements are eligible, but patients will be asked to avoid their use after on study
* Current or recent use (within 6 months of registration or baseline mammogram, whichever is first) of any of the following: hormonal forms of contraception (includes oral, transdermal, implanted, and injectable formulations): selective estrogen receptor modifiers; aromatase inhibitors; GnRH analogs; androgens or antiandrogens
* Concurrent use of warfarin and strong inhibitors or CYP2D6 will not be allowed
* A personal history or a strong family of thromboembolism, including deep venous thrombosis (DVT), pulmonary embolus (PE), or cerebrovascular accident (CVA); a personal history of transient ischemic attack (TIA) or retinal vein thrombosis will also not be allowed; in addition, patients with a condition known to increase hypercoagulability, such as Factor V Leiden disease, will be excluded; patients with atrial fibrillation will be excluded, due to risk of CVA, but patients with coronary artery disease or congestive heart failure without atrial fibrillation will be allowed to participate
* Current intrauterine pregnancy or plans to become pregnant within two years; in addition, currently nursing mothers will be excluded
* Serum creatinine \> 2X the institutional norm
* Total bilirubin \> 2X the institutional norm
* Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) \> 2X the institutional norm
* Unable to provide consent
Minimum Eligible Age

25 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

City of Hope National Medical Center

OTHER

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role collaborator

Wake Forest University

OTHER

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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Smitia Bhatia

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Smita Bhatia, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

City of Hope Medical Center

Duarte, California, United States

Site Status

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

MD Anderson

Houston, Texas, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University Health Network, Toronto

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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R01CA140245-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2010-01976

Identifier Type: REGISTRY

Identifier Source: secondary_id

08218

Identifier Type: -

Identifier Source: org_study_id

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