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Acolbifene in Preventing Cancer in Premenopausal Women at High Risk of Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00853996
First received: February 26, 2009
Last updated: May 31, 2013
Last verified: May 2013
  Purpose

This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or coming back.


Condition Intervention Phase
Breast Cancer
Drug: acolbifene hydrochloride
Other: questionnaire administration
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Study of Acolbifene in Pre-Menopausal Women at High Risk for Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Reduced proliferation as measured by Ki-67 expression in breast epithelial cells obtained by random periareolar fine needle aspiration [ Time Frame: At 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in mammographic breast density [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • Change in IGF-1 and ratio of IGF-1 to its binding protein [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • Change in ER expression [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • Change in hot flashes as assessed by the Loprinzi hot flash scoring system [ Time Frame: Baseline to up to 2 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in muscle/joint complaints as assessed by the validated HAQ II questionnaire [ Time Frame: Baseline to up to 2 weeks post-treatment ] [ Designated as safety issue: No ]
  • Change in fatigue symptoms as assessed by the Brief Fatigue Inventory [ Time Frame: Baseline to up to 2 weeks post-treatment ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: February 2009
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prevention (acolbifene hydrochloride)
Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity.
Drug: acolbifene hydrochloride
Given orally
Other Names:
  • EM-652.HCL
  • SCH 57068.HCl
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the effect of six months of acolbifene 20 mg/day on Ki-67 in high risk premenopausal women with baseline hyperplasia +/- atypia and Ki-67 positivity of >= 2%..

SECONDARY OBJECTIVES:

I. To determine the effect of six months of acolbifene 20 mg/day on mammographic breast density in high risk premenopausal women.

II. To determine the effect of six months of acolbifene 20 mg/day on serum levels of follicular phase bioavailable estradiol, and luteal phase progesterone, testosterone, and fasting IGF-1/IGFBP-3.

III. To determine the effect of six months of acolbifene 20 mg/day on epithelial cell cytomorphology and molecular markers such as ER, PgR, and pS2.

IV. To determine the effect of six months of acolbifene on markers of cardiovascular risk (C-reactive protein, functional AntiThrombin III, and fasting lipid profile) and bone turnover markers associated with bone mineral density gain or loss (serum osteocalcin and N-telopeptide crosslinks).

V. To assess any increase in reported hot flashes, menstrual cycle irregularities, pelvic pain, musculoskeletal complaints, and fatigue from baseline.

OUTLINE:

Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity.

Patients undergo symptom assessment (hot flashes, menstrual abnormalities, pelvic pain, muscle and joint pain, and fatigue) at baseline, 6-8 weeks, monthly for 6 months, and then at 2 weeks after completion of study treatment.

Patients undergo random periareolar fine needle aspiration between days 1-10 of menstrual cycle at baseline and at 6 months. Patients also undergo blood sample collection between days 1-10 and days 20-24 of menstrual cycle at baseline and at 6 months. Samples taken between days 1-10 of menstrual cycle are analyzed for Ki-67 expression, cytomorphology, molecular markers (estrogen receptor, progesterone receptor, and pS2 expression), and bioavailable estradiol levels. Samples taken between days 20-24 of menstrual cycle are analyzed for progesterone, testosterone, IGF-1, IGFBP-3, lipid profile, bone-turnover markers (osteocalcin and N-telopeptide crosslinks), C-reactive protein, and functional antithrombin III.

After completion of study treatment, patients are followed at 2 weeks.

  Eligibility

Ages Eligible for Study:   30 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • At increased risk for breast cancer, as indicated by >= 1 of the following risk factors:
  • BRCA1/2 mutation characterized as deleterious or of uncertain significance
  • Prior atypical ductal hyperplasia, ductal carcinoma in situ, or lobular carcinoma in situ
  • Prior random periareolar fine needle aspiration (RPFNA) showing atypical hyperplasia
  • Family history consistent with hereditary breast cancer, as indicated by 1 of the following criteria:

    • >= 4 relatives with breast cancer
    • >= 2 relatives diagnosed with breast cancer at ≤ 50 years of age
    • Breast and ovarian cancer diagnosed in same relative
  • No suspicion for breast cancer on baseline mammogram performed between days 1-10 of menstrual cycle within 3 months prior to screening baseline RPFNA
  • Exhibits hyperplasia with or without atypia (Masood score >= 14) with >= 500 cells AND Ki-67 positivity >= 2% by RPFNA performed within 6 months prior to initiation of study drug
  • Estimated visual mammographic breast density category >= 5% on mammogram performed within 6 months prior to initiation of study drug
  • Has regular menstrual cycles (between 21 and 35 days) unless using extended regimen oral contraceptives or a contraceptive device (e.g., Mirena IUD)
  • Absolute granulocyte count > 1,000/mm^3
  • Platelets > 100,000/mm^3
  • Hemoglobin > 10 g/dL
  • Bilirubin < 2.0 mg/dL
  • AST < 2 times upper limit of normal (ULN)
  • Albumin > 3.0 g/dL
  • Creatinine < 1.5 mg/dL
  • Not pregnant or nursing
  • No nursing within the past 6 months
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • Willing to ingest recommended dose of calcium and vitamin D for premenopausal bone health (1,200 mg calcium and 800 IU vitamin D daily)
  • Alkaline phosphatase < 2 times ULN
  • No known osteoporosis or severe osteopenia (T-score -2 or worse by DEXA)
  • No history of symptomatic endometriosis with pelvic pain, poorly controlled migraines, or hot flashes
  • No history of deep venous thrombosis
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to the study agent
  • No other condition or concurrent illness that, in the opinion of the investigator, would make the patient a poor candidate for RPFNA
  • At least 1 year since prior and no concurrent aromatase inhibitors (e.g., anastrozole, exemestane, or letrozole) or selective estrogen receptor modulators (e.g., tamoxifen citrate, raloxifene, or arzoxifene hydrochloride)
  • Concurrent hormonal contraceptives allowed provided patient remains on the same hormonal regimen from 3 months prior to baseline aspiration until the completion of study treatment
  • No other concurrent chemopreventive agents
  • No concurrent anticoagulants
  • Gail risk >= 1.7% and/or relative risk >= 3 times that for 5-year age group
  • No other concurrent investigational agents
  • Premenopausal
  • No bilateral breast implants
  • More than 6 months since initiating or discontinuing oral contraceptives
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853996

Locations
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Sponsors and Collaborators
Investigators
Principal Investigator: Carol Fabian University of Kansas
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00853996     History of Changes
Obsolete Identifiers: NCT00855751
Other Study ID Numbers: NCI-2009-01116, KUMC HSC 10588, CDR0000681103, CO08101, UW105-6-01, HSC 10588, N01CN35153
Study First Received: February 26, 2009
Last Updated: May 31, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 26, 2014