Retinoid 9cUAB30 in Producing a Biologic Effect in Patients With Early Stage Breast Cancer

NCT ID: NCT02876640

Last Updated: 2024-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-16
• Study Completion Date: 2022-06-03

Brief Summary

This phase 1b trial studies the biologic effect of 9cUAB30 on early stage breast cancer. 9cUAB30 is a retinoid X receptor (RXR)-selective retinoid that acts in a tissue selective manner with the goal of minimizing side effects, a necessary feature of agents under development for cancer prevention.

Detailed Description

PRIMARY OBJECTIVE:

I. Compare molecular analysis of pre- and post-treatment tissue samples of breast cancers of patients treated with 14-28 days of oral retinoid X receptor (RXR)-selective retinoid 9cUAB30 (9 cUAB30) will demonstrate significantly reduced proliferation.

SECONDARY OBJECTIVES:

I. Determine if 14-28 days of oral RXR-selective 9c-UAB30 treatment increases apoptotic index, as measured by cleaved caspase 3 assay.

II. Examine the differences in gene expression from baseline to post-exposure breast cancer samples using a custom gene panel from Nanostring Technologies.

III. To examine if the maximum concentration (Cmax) and safety of 9cUAB30 in the first 5 participants is affected by reducing the number of capsules at the 240 mg dose level.

IV. To examine the Cmax of all participants at baseline and on the day of surgery.

V. Determine if treatment with 2-4 weeks of 9cUAB30 prior to surgery will increase gene expression of type I immune cells in the tumor immune environment of all participants except the first 5.

VI. Assess the overall safety of 9cUAB30 in comparison with known retinoid toxicity.

EXPLORATORY OBJECTIVE:

I. Determine if treatment with 2-4 weeks of 9cUAB30 prior to surgery will increase activated type I dendritic cells in peripheral blood.

OUTLINE:

Patients receive retinoid 9cUAB30 orally (PO) once daily (QD) for 14 to 28 days. Patients then undergo tumor resection surgery. Patients undergo blood and urine sample collection throughout the study.

After completion of study treatment, patients are followed up at 7 days and 4-5 weeks.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Breast Ductal Carcinoma In Situ; Early Stage Breast Carcinoma; Invasive Breast Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Treatment (retinoid 9cUAB30)

Patients receive retinoid 9cUAB30 PO QD for 14 to 28 days. Patients then undergo tumor resection surgery. Patients undergo blood and urine sample collection throughout the study.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood and urine sample collection

Retinoid 9cUAB30

Intervention Type: DRUG

Given PO

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo tumor resection surgery

Interventions

Biospecimen Collection

Undergo blood and urine sample collection

Intervention Type: PROCEDURE

Retinoid 9cUAB30

Given PO

Intervention Type: DRUG

Therapeutic Conventional Surgery

Undergo tumor resection surgery

Intervention Type: PROCEDURE

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; (9Z)-UAB-30; 9cUAB30; UAB-30

Eligibility Criteria

Inclusion Criteria

• Female only. The sample size of males affected by breast cancer is limited, hence we will not be able to collect significant data for analysis of the effect of study drug on breast cancer in males
• Age >= 18 years. Because no dosing or adverse event data is currently available on the use of 9cUAB30 in participants <18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70%
• Invasive breast cancer diagnosed by needle core biopsy between 0.5 cm and 5 cm in size based on imaging, that is estrogen receptor positive (ER+) or estrogen receptor negative (ER-), Her2neu positive or negative OR ductal carcinoma in situ (DCIS) of the breast diagnosed by core needle biopsy and at least 1.0 cm in size based on imaging. Grade 3 ER+ DCIS will be allowed as well as ER- DCIS of any grade. For DCIS-only lesions, the imaging abnormality corresponding to the cancer must be at least 1.0 cm in size (i.e. calcifications, distortion or mass on mammogram, or mass or non-mass enhancement on magnetic resonance imaging [MRI])
• White blood cells (WBC) >= 3000/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin > 10 g/dL
• Bilirubin =< upper limit of institutional normal
• Aspartate aminotransferase (AST) =< upper limit of institutional normal
• Creatinine =< upper limit of institutional normal
• Triglycerides =< 1.5 x upper limit of normal (ULN)
• Cholesterol =< 1.5 x ULN
• Participants must agree to discontinue all supplements containing vitamin A while taking study medication and for thirty days after the last dose of study medication.
• Have not been treated with chemotherapy, or biological therapy in the last 5 years. We do not know if the previous treatment will have an effect on the tissues to be examined.
• Have not used tamoxifen, raloxifene, or other antiestrogen compounds within 6 months of study entry. If used within 5 years of study entry, total duration of use must be less than 6 months
• Have not used exogenous hormone replacement therapy or hormonal contraception in the year prior to diagnosis. The use of non-systemic estrogen (such as vaginal estrogen use) is allowed
• The effects of 9cUAB30 on the developing human fetus are unknown. Since retinoids are known to be teratogenic, to avoid any complications due to unintentional pregnancies only postmenopausal women and some premenopausal women (as outlined below) will be eligible; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

• Women will be considered postmenopausal if one of the following is met:

• Prior bilateral oophorectomy
• 60 years of age or older
• Age less than 60 years; amenorrheic for 12 or more months; and follicle stimulating hormone (FSH) in the postmenopausal range
• Premenopausal women without childbearing potential are eligible to participate if one of the following criteria is met:

• Prior hysterectomy
• Prior fallopian tubal ligation (cut, tied, or sealed)
• Prior placement of permanent intratubal contraceptive devices (e.g. Essure)
• Partner with prior vasectomy and willing to use barrier method (e.g. condoms)
• Participants must have the ability to understand, and the willingness to sign, a written informed consent document

Exclusion Criteria

• Participant taking medications that might interact with 9cUAB30
• Participant who has started or increased dosage of lipid-lowering agents in the last 30 days of enrollment
• Participant receiving any other investigational agents within 30-days of enrollment nor during study participation with the exception of 18F-FFNP investigational imaging agent
• Participant with a history of allergic reactions attributed to compounds of similar chemical or biologic composition of retinoids
• Participant with an uncontrolled intercurrent illness including, but not limited to;

• Ongoing or active infection,
• Symptomatic congestive heart failure,
• Unstable angina pectoris,
• Cardiac arrhythmia,
• A persistent grade 3 hypertension

• For grade 1, grade 2, and non-persistent grade 3 hypertension, repeat blood pressure reading after 5 minutes. If the average reading of the two measurements is grade 3 (systolic BP >=160 mm Hg or diastolic BP >=100 mm Hg) the patient is not eligible. If the average reading of the two measurements is less than or equal to grade 2, then the participant is eligible. If the average of the 2 readings is grade 1 or grade 2 hypertension, document the appropriate level hypertension on the baseline symptom form.
• Psychiatric illness/social situations that will limit compliance with study requirements
• Participant who is breastfeeding or planning to breastfeed for a month post last dose of study agent
• Participant known to be human immunodeficiency virus (HIV)-positive, as we do not know the effects of study drug on suppression of the immune system.
• Participant with a history of a second cancer diagnosis or reoccurrence < 2 years from study entry with the exception of a history of squamous or basal cell carcinoma of the skin < 2 years from study entry will not be excluded from this study. This is to eliminate the residual effects of any previous treatments for those cancers
• Participant with history of ipsilateral breast radiation
• Participant's core biopsy slides suggest that later re-sectioning will not contain sufficient tumor to allow for an adequate evaluation of Ki67 and caspase 3 assays, at a minimum

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helen Krontiras

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Northwestern University

Chicago, Illinois, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Countries

United States

References

Thomas PS, Patel AB, Lee JJ, Liu DD, Hernandez M, Muzzio M, Contreras A, Sepeda V, Mays C, Weber D, Vornik LA, Khan SA, Dimond E, Heckman-Stoddard BM, Perloff M, Brown PH. Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer. Cancer Prev Res (Phila). 2023 Jan 4;16(1):47-55. doi: 10.1158/1940-6207.CAPR-22-0210.

Reference Type: DERIVED

PMID: 36228112 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2016-01293

Identifier Type: REGISTRY

Identifier Source: secondary_id

N01-CN-2012-00033

Identifier Type: -

Identifier Source: secondary_id

UW16063

Identifier Type: OTHER

Identifier Source: secondary_id

UWI2015-05-01

Identifier Type: OTHER

Identifier Source: secondary_id

N01CN00033

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014520

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2016-01293

Identifier Type: -

Identifier Source: org_study_id