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

NCT03323658 | Completed Phase 1 Results DMC FDA Drug

• 6 other identifiers: NCI-2017-01960N01-CN-2012-000342017-0911MDA2016-08-02N01CN00034P30CA016672
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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. Bexarotene belongs to a class of drugs that are called rexinoids, and it may reduce the incidence of breast tumors.

Conditions

Breast Atypical Ductal Hyperplasia; Breast Atypical Lobular Hyperplasia; Breast Ductal Carcinoma In Situ; Breast Lobular Carcinoma In Situ; Invasive Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Baseline up to 28 days

• Number of Participants With Trace Level of Bexarotene Concentration in Plasma Detected

  baseline and end of treatment, up to 4 weeks

• Number of Participants With Bexarotene Concentration in Tissue

  end of treatment, up to 4 weeks

Other Outcomes (1)

• Tissue Markers

  baseline, 15, and Day 28 visits

Study Arms (1)

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.

Drug: Bexarotene; Other: Questionnaire Administration

Interventions

Bexarotene DRUG

Given topically

Also known as: 3-methyl TTNEB, LGD1069, Targretin

Prevention (bexarotene)

Questionnaire Administration OTHER

Ancillary studies

Prevention (bexarotene)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 (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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ

Interventions

Bexarotene

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Priya Thomas,MD-Associate Professor, Clinical Cancer Prevention
• Organization: UT MD Anderson Cancer Center

psthomas@mdanderson.org

(713) 745-1075

Study Officials

• Parijatham (Priya) S Thomas

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2017
• First Posted: October 27, 2017
• Study Start: June 15, 2018
• Primary Completion: August 3, 2021
• Study Completion: March 25, 2022
• Last Updated: January 10, 2023
• Results First Posted: December 6, 2022

Record last verified: 2022-11

Locations

US (1)