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

NCT01196936 | Active Not Recruiting Phase 2 Results DMC

• 3 other identifiers: 08218R01CA140245-01NCI-2010-01976
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 13

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Cancer survivors; Low Dose Tamoxifen; Breast Cancer Risk Reduction

Outcome Measures

Primary Outcomes (1)

• Mammographic Breast Density

  Mammographic density was quantified as percentage of fibroglandular tissue. Using an intention-to-treat analysis, mammographic breast density (MBD) was compared between patients in the low dose tamoxifen intervention and placebo group by applying the linear mixed effects model for normally distributed data.

  At year two post treatment

Secondary Outcomes (8)

• Insulin Growth Factor Levels (IGF1)

  Up to 2 years

• Number of Grade 2-4 Toxicities

  Up to 2 years

• Biomarker Levels

  Up to 2 years

• Percentage of Pills Taken Out of the Total Prescribed

  Up to 2 years

• Number of Participants With Different Patient Reported Symptoms, Measured by Questionnaire

  Up to 2 years

Study Arms (2)

Arm I (tamoxifen citrate)

EXPERIMENTAL

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

Drug: Tamoxifen Citrate; Procedure: Digital mammography; Other: immunohistochemistry staining method; Other: pharmacological study; Other: laboratory biomarker analysis; Genetic: protein expression analysis; Other: pharmacogenomic studies; Other: questionnaire administration; Procedure: Fine needle aspiration; Other: Quality of Life Assessment

Arm II (placebo)

PLACEBO COMPARATOR

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

Drug: Placebo; Procedure: Digital mammography; Other: immunohistochemistry staining method; Other: pharmacological study; Other: laboratory biomarker analysis; Genetic: protein expression analysis; Other: pharmacogenomic studies; Other: questionnaire administration; Procedure: Fine needle aspiration; Other: Quality of Life Assessment

Interventions

Digital mammography PROCEDURE

Correlative studies

Arm I (tamoxifen citrate); Arm II (placebo)

pharmacological study OTHER

Correlative Studies

Arm I (tamoxifen citrate); Arm II (placebo)

laboratory biomarker analysis OTHER

Correlative Studies

Arm I (tamoxifen citrate); Arm II (placebo)

protein expression analysis GENETIC

correlative studies

Arm I (tamoxifen citrate); Arm II (placebo)

pharmacogenomic studies OTHER

correlative studies

Arm I (tamoxifen citrate); Arm II (placebo)

questionnaire administration OTHER

Ancillary studies

Arm I (tamoxifen citrate); Arm II (placebo)

Tamoxifen Citrate DRUG

5 mg PO Daily

Also known as: Marketed under trade name Nolvadex as 10 mg and 20 mg tablets, ICI 46,474

Arm I (tamoxifen citrate)

Placebo DRUG

1 tablet daily

Arm II (placebo)

immunohistochemistry staining method OTHER

Correlative Studies

Arm I (tamoxifen citrate); Arm II (placebo)

Fine needle aspiration PROCEDURE

Also known as: Correlative studies

Arm I (tamoxifen citrate); Arm II (placebo)

Quality of Life Assessment OTHER

Ancillary Studies

Arm I (tamoxifen citrate); Arm II (placebo)

Eligibility Criteria

• Age: 25 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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: 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: collaborator
• University of Chicago: collaborator
• University of Minnesota: collaborator
• University of Colorado, Denver: collaborator
• Wake Forest University: collaborator
• University of Alabama at Birmingham: lead
• National Cancer Institute (NCI): collaborator
• St. Jude Children's Research Hospital: collaborator
• University Health Network, Toronto: collaborator
• University of Michigan: collaborator
• Dana-Farber Cancer Institute: collaborator
• Mayo Clinic: collaborator
• University of Washington: collaborator
• City of Hope National Medical Center: collaborator

Study Sites (13)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5718, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University Health Network, Toronto

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen; Immunohistochemistry; Pharmacogenomic Testing; Biopsy, Fine-Needle

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Genetic Testing; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Biopsy, Needle; Biopsy; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures

Limitations and Caveats

Slower than expected accrual, and financial constraints of supporting the study drug costs necessitated study closure before attainment of planned study enrollment.

Results Point of Contact

• Title: Dr. Smita Bhatia
• Organization: University of Alabama at Birmingham

sbhatia@peds.uab.edu

(205) 638-2120

Study Officials

• Smita Bhatia, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 9, 2010
• Study Start: September 1, 2010
• Primary Completion: December 11, 2018
• Study Completion (Estimated): December 11, 2028
• Last Updated: January 5, 2026
• Results First Posted: January 27, 2020

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (12)