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Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer

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ClinicalTrials.gov Identifier: NCT03323658
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 26, 2017
First Posted Date  ICMJE October 27, 2017
Last Update Posted Date October 7, 2019
Actual Study Start Date  ICMJE June 15, 2018
Estimated Primary Completion Date August 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2017)
Incidence of adverse events [ Time Frame: Up to 30 days after completion of study drug ]
Will be assessed by Common Terminology Criteria for Adverse Events criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03323658 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2018)
  • Changes in markers of systemic toxicity [ Time Frame: Baseline up to 28 days ]
    Serum biomarkers to be tested will be total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, thyroid-stimulating hormone, T4, T3, and calcium. Will be summarized using mean, standard deviation and median (range) for continuous variables at each time point. Wilcoxon rank-sum test may be used to examine the difference of continuous variables between participants' characteristics groups. Will be plotted as functions of time (baseline, week 1, week 2, and week 4). Linear mixed effect model will be applied to model the biomarker change over time for all participants. Appropriate transformation and regression model will be used to ensure the model fit.
  • Bexarotene concentration [ Time Frame: Up to 30 days after completion of study drug ]
    Will be determined using liquid chromatography-mass spectrometry (MS)/MS. Will be summarized using mean, standard deviation and median (range) for continuous variables at each time point. Wilcoxon rank-sum test may be used to examine the difference of continuous variables between participants' characteristics groups. Will be plotted as functions of time (baseline, week 1, week 2, and week 4). Linear mixed effect model will be applied to model the biomarker change over time for all participants. Appropriate transformation and regression model will be used to ensure the model fit. Will be calculated along with a 95% confidence interval.
  • Tissue markers [ Time Frame: Up to 28 days ]
    One of the four cores collected from the core biopsies from baseline (in dose expansion cohort only) and post treatment (all dose expansion cohort participants and optional for dose escalation group) will be formalin-fixed and paraffin embedded (FFPE) for histological analysis. One of the four cores collected from the core biopsies from baseline and post treatment will be placed in RNALater and utilized for gene expression of ribonucleic acid (RNA) biomarkers. Gene expression will be performed.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2017)
  • Bexarotene concentration [ Time Frame: Up to 30 days after completion of study drug ]
    Will be determined using liquid chromatography-mass spectrometry (MS)/MS. Will be summarized using mean, standard deviation and median (range) for continuous variables at each time point. Wilcoxon rank-sum test may be used to examine the difference of continuous variables between participants' characteristics groups. Will be plotted as functions of time (baseline, week 1, week 2, and week 4). Linear mixed effect model will be applied to model the biomarker change over time for all participants. Appropriate transformation and regression model will be used to ensure the model fit. Will be calcul
  • Change in Ki-67 and cyclin D1 expression in tissue [ Time Frame: Baseline up to 30 days after completion of study drug ]
    Will be assessed by immunohistochemistry. Will be summarized using mean, standard deviation and median (range) for continuous variables at each time point. Wilcoxon rank-sum test may be used to examine the difference of continuous variables between participants' characteristics groups. Will be plotted as functions of time (baseline, week 1, week 2, and week 4). Linear mixed effect model will be applied to model the biomarker change over time for all participants. Appropriate transformation and regression model will be used to ensure the model fit.
  • Changes in markers of systemic toxicity [ Time Frame: Baseline up to 28 days ]
    Serum biomarkers to be tested will be total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, thyroid-stimulating hormone, T4, T3, and calcium. Will be summarized using mean, standard deviation and median (range) for continuous variables at each time point. Wilcoxon rank-sum test may be used to examine the difference of continuous variables between participants' characteristics groups. Will be plotted as functions of time (baseline, week 1, week 2, and week 4). Linear mixed effect model will be applied to model the biomarker change over time for all participants. A
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer
Official Title  ICMJE A Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer
Brief Summary This phase I trial studies the side effects and best dose of bexarotene in preventing breast cancer in patients at high risk for breast cancer.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose of topical bexarotene 1% (weight by weight [w/w]) gel for evaluation in healthy women. (Dose Escalation Group) II. Conduct an intervention of topical 1% bexarotene gel to an unaffected breast of healthy women at high risk for breast cancer for 4 weeks at the maximum tolerated dose (MTD) as determined during the dose escalation group phase to assess bexarotene concentration in the breast tissue. (Dose Expansion Group)

SECONDARY OBJECTIVES:

I. To detect bexarotene concentration in the serum at baseline and at 4 weeks of treatment.

II. To detect bexarotene concentration in the breast tissue at 4 weeks of treatment in the dose escalation group.

III. To investigate the effects of topical bexarotene on serum biomarkers. IV. To investigate the biologic effects of topical bexarotene 1% gel in the breast tissue, we will determine the change from baseline in i) lipid biomarkers (total cholesterol, triglycerides, low density lipoprotein [LDL], high density lipoprotein [HDL]), ii) thyroid function biomarkers (thyroid stimulating hormone [TSH], T4, T3), iii) calcium.

TERTIARY OBJECTIVES:

I. To examine changes in gene expression associated with retinoid action. (Dose Expansion Group)

OUTLINE: This is a dose-escalation study.

Group 1 will apply 10mg bexarotene topically to one breast every other day (QOD) for 4 weeks; Group 2 will apply 10mg bexarotene topically to one breast every other day (QOD) for 1 week and then daily for 3 weeks after confirmation that toxicity is at an acceptable range; Group 3 will apply 10mg bexarotene topically to one breast every other day (QOD) for 1 week, then daily for 1 week, and then 20mg daily for 2 weeks after confirmation that toxicity is at an acceptable range.

After completion of study treatment, patients are followed up at 30 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Atypical Ductal Breast Hyperplasia
  • Atypical Lobular Breast Hyperplasia
  • Ductal Breast Carcinoma In Situ
  • Invasive Breast Carcinoma
  • Lobular Breast Carcinoma In Situ
Intervention  ICMJE
  • Drug: Bexarotene
    Given topically
    Other Names:
    • 3-methyl TTNEB
    • LGD1069
    • Targretin
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE Experimental: Prevention (bexarotene)
Group 1 will apply 10mg bexarotene topically to one breast QOD for 4 weeks; Group 2 will apply 10mg bexarotene topically to one breast QOD for 1 week and then daily for 3 weeks after confirmation that toxicity is at an acceptable range; Group 3 will apply 10mg bexarotene topically to one breast QOD for 1 week, then daily for 1 week, and then 20mg daily for 2 weeks after confirmation that toxicity is at an acceptable range.
Interventions:
  • Drug: Bexarotene
  • Other: Laboratory Biomarker Analysis
  • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 26, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2020
Estimated Primary Completion Date August 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants must be at high risk as defined by a history of breast cancer (invasive or ductal breast carcinoma in situ [DCIS]) and be at least 5 years out from diagnosis, or lobular carcinoma in situ (LCIS), or proliferative benign breast disease such atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH) or genetic test confirmation of BRCA 1/2 mutation carrier or have a breast cancer risk assessment >= 1.7% in 5 years or a lifetime risk >= 20%
  • No evidence of disease (in situ or invasive cancer that would normally be treated by resection) at trial entry as determined by the investigator; diagnosis of invasive cancer must be at least 5 years prior to initiation on trial
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/microliter
  • Absolute neutrophil count >= 1,500/microliter
  • Platelets >= 100,000/microliter
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal (ULN)
  • Creatinine =< 1.5 x institutional ULN
  • Hemoglobin >= 10 g/dL
  • Thyroid-stimulating hormone (TSH) within normal institutional limits
  • Triglycerides =< 300 mg/dl
  • Total cholesterol =< 300 mg/dl
  • >= 6 months from all previous breast cancer treatment (including endocrine therapy)
  • Participants must have adequate accessible breast tissue as determined by the treating physician, consisting of one breast unaffected by invasive cancer, which has not been radiated; a history of benign core biopsy of this breast will be permitted
  • Participants need to have had any breast imaging with a normal/benign (bi-rads 1 or 2) result within 180 days of day 0 and no further routine breast imaging planned during the course of the study (4 weeks); exception: if the mammogram result was a bi-rads 0 and the imaging work-up (ultrasound and/or magnetic resonance imaging [MRI]) result comes back normal/benign (bi-rads 1 or 2) before treatment initiation, then participant is eligible.
  • For women of childbearing potential; negative pregnancy testing within 72 hours prior to or on study visit #1 (day 0) and willingness to use adequate contraception during the study intervention; OR post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of menstrual period for 2 years in women with a prior history of chemotherapy exposure who were pre-menopausal prior to chemotherapy; in women of childbearing potential, effective contraception must be used for one month prior to the initiation of therapy, during therapy, and for at least one month following discontinuation of therapy; it is recommended that two reliable forms of contraception be used simultaneously; if participants are interested in enrolling and have not met the requirement for contraception, they will be seen in the clinic in 1 month for re-evaluation once they have met this requirement and ensure all other eligibility criteria is met prior to dose assignment
  • Willingness to comply with all study interventions and follow-up procedures including the ability to apply the study drug to the breast
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability to avoid exposure of the treated breast area to sunlight and artificial ultraviolet light during the use of bexarotene gel

Exclusion Criteria:

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to bexarotene gel, oral or topical retinoids
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, thromboembolic disease, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant, or had given birth, or nursed at any time during the last 12 months
  • Women with a history of any cancer within the last 3 years, except for non-melanoma skin cancer; history of breast cancer must be at least > 5 years from diagnosis
  • Prior bilateral breast surgery (mastectomy, segmental mastectomy, or breast augmentation surgery including breast implants or breast reductions) or combination of breast radiation and surgery involving both breasts
  • Prior history or evidence of metastatic breast cancer
  • Prior history of histologically confirmed bilateral invasive breast cancer
  • Current use or < 6 months since use of selective estrogen receptor modulator (SERMS) or aromatase inhibitors or any other investigational treatment for breast cancer prevention or therapy
  • Skin lesions that disrupt the stratum corneum (eg., eczema, ulceration) or any breakdown of the skin
  • Current use of a retinol containing agent or any retinoid analogue drug within the last 30 days
  • Dietary vitamin A intake >= 5,000 IU/day (as determined by dietary supplementation)
  • Treatment with any investigational drug or investigational biologic within 30 days of initiating study treatment or during the study
  • History of human immunodeficiency virus (HIV) or active hepatitis C
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03323658
Other Study ID Numbers  ICMJE NCI-2017-01960
NCI-2017-01960 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00034
2017-0911 ( Other Identifier: M D Anderson Cancer Center )
MDA2016-08-02 ( Other Identifier: DCP )
N01CN00034 ( U.S. NIH Grant/Contract )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Parijatham (Priya) S Thomas M.D. Anderson Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP