Breast Atypical Ductal HyperplasiaPhase 1NCT03323658
Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer
A Phase 1 study testing Bexarotene and Questionnaire Administration in people with Breast Atypical Ductal Hyperplasia and Breast Atypical Lobular Hyperplasia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Bexarotene belongs to a class of drugs that are called rexinoids, and it may reduce the incidence of breast tumors. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Atypical Ductal Hyperplasia, Breast Atypical Lobular Hyperplasia, Breast Ductal Carcinoma In Situ
- What is being tested?
- Bexarotene and Questionnaire Administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jun 2018to 25 Mar 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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 (e.g., 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer
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. Bexarotene belongs to a class of drugs that are called rexinoids, and it may reduce the incidence of breast tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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, 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.
EXPLORATORY OBJECTIVE:
- 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.
- Conditions
- Breast Atypical Ductal Hyperplasia, Breast Atypical Lobular Hyperplasia, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ, Invasive Breast Carcinoma
- Being tested
- Bexarotene, Questionnaire Administration
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating, Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BexaroteneDrug
Also called 3-methyl TTNEB, LGD1069, Targretin
Given topically
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Prevention (bexarotene) | Experimental | 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. Receives: Drug: Bexarotene; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
Dose Limiting Toxicity (DLT) is defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. In addition, a DLT will be a grade 2 skin adverse event that recurs and persists for at least 3 days.
Measured: 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
Secondary outcomes (3)
Number of Participants With Changes in Markers of Systemic Toxicity
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.
Measured: Baseline up to 28 days
Number of Participants With Trace Level of Bexarotene Concentration in Plasma Detected
Plasma concentrations of bexarotene were evaluated in all participants at baseline and at end of study. Plasma samples: ND = Not detected (below the quantitation limit of 0.5 ng/mL) TDL = Trace levels detected (below the LOQ of 0.5ng/mL; estimated value)
Measured: baseline and end of treatment, up to 4 weeks
Number of Participants With Bexarotene Concentration in Tissue
Breast tissue concentrations were available only in those women who underwent breast biopsies. Tissue samples: Not detected (below the quantitation limit of 2.5 ng/g for a 10mg sample) and Trace levels detected (below the LOQ of 2.5ng/g; estimated value).
Measured: end of treatment, up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study start15 Jun 2018
- Primary completion3 Aug 2021
- Study completion25 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast Atypical Ductal HyperplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Parijatham (Priya) S Thomas, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03323658
- Sponsor's protocol ID
- NCI-2017-01960
- Other IDs
- NCI-2017-01960, N01-CN-2012-00034, 2017-0911, MDA2016-08-02, N01CN00034, P30CA016672
- Status last verified
- Nov 2022
- First submitted
- 26 Oct 2017
- Last updated
- 10 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer
- ClinicalTrials.gov ID
- NCT03323658
- Acronym / sponsor ID
- NCI-2017-01960
- Conditions
- Breast Atypical Ductal Hyperplasia, Breast Atypical Lobular Hyperplasia, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ, Invasive Breast Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Jun 2018 (actual)
- Primary completion
- 3 Aug 2021 (actual)
- Study completion
- 25 Mar 2022 (actual)
- First posted
- 27 Oct 2017 (actual)
- Results
- Posted 6 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. Bexarotene belongs to a class of drugs that are called rexinoids, and it may reduce the incidence of breast tumors.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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, 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.
EXPLORATORY OBJECTIVE:
- 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 design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prevention (bexarotene) | Experimental | Drug: Bexarotene, Other: Questionnaire AdministrationGroup 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BexaroteneAlso: 3-methyl TTNEB, LGD1069, TargretinGiven topically | Drug | Prevention (bexarotene) |
| Questionnaire AdministrationAncillary studies | Other | Prevention (bexarotene) |
Primary outcome
Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)
Time frame: 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments
Dose Limiting Toxicity (DLT) is defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. In addition, a DLT will be a grade 2 skin adverse event that recurs and persists for at least 3 days.
3 secondary outcomes
Number of Participants With Changes in Markers of Systemic Toxicity
Time frame: Baseline up to 28 days
Number of Participants With Trace Level of Bexarotene Concentration in Plasma Detected
Time frame: baseline and end of treatment, up to 4 weeks
Number of Participants With Bexarotene Concentration in Tissue
Time frame: end of treatment, up to 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Breast Atypical Ductal Hyperplasia
Active, not recruitingPhase 3
Metformin Hydrochloride in Preventing Breast Cancer in Patients With Atypical Hyperplasia or In Situ Breast Cancer
Breast Atypical Ductal Hyperplasia, Breast Ductal Carcinoma In Situ
RecruitingPhase 2
Low Dose Tamoxifen With or Without Omega-3 Fatty Acids for Breast Cancer Risk Reduction
Breast Atypical Hyperplasia, Breast Carcinoma
RecruitingPhase 2
Finding the Best Tamoxifen Dose for Breast Cancer Risk Reduction in Premenopausal Women, RENAISSANCE Trial
Breast Atypical Ductal Hyperplasia, Breast Atypical Lobular Hyperplasia
RecruitingPhase 2
Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer
Breast Atypical Hyperplasia, Breast Carcinoma
RecruitingObservational study
Impact of Dietary Inflammatory Potential on Breast Cancer Risk
Breast Atypical Ductal Hyperplasia, Breast Atypical Lobular Hyperplasia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parijatham (Priya) S Thomas principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bexarotene and Questionnaire Administration in people with Breast Atypical Ductal Hyperplasia and Breast Atypical Lobular Hyperplasia, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities) (time frame: 4 weeks of treatment, Up to 30 days after completion of study drug for AE assessments). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2023.