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

NCT02876640 | Terminated Phase 1 Results DMC FDA Drug

• 6 other identifiers: NCI-2016-01293N01-CN-2012-00033UW16063UWI2015-05-01N01CN00033P30CA014520
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (1)

• Absolute Change in Ki-67 Expression in Breast Epithelial Cells of Patients Treated With 9cUAB30

  Ki-67 was analyzed using immunohistochemistry. Absolute change was measured in looking at the baseline in comparison to that at the end of treatment.

  Baseline up to 28 days (post-exposure)

Secondary Outcomes (6)

• Change in Apoptosis in Breast Epithelial Cells of Patients Treated With 9cUAB30

  Baseline up to 28 days (post-exposure)

• Change in Gene Expression of Breast Cancer Samples Using a Custom Gene Panel From Nanostring Technologies

  Baseline up to 28 days (post-exposure)

• Change in Maximum Concentration (Cmax)

  Pre-dose, 5 minutes, and 2 hours post-dose

• Incidence of Observed Adverse Events

  Up to 28 days

• Change in Activated Type I Dendritic Cells in Peripheral Blood

  Baseline up to 28 days (post-exposure)

Study Arms (1)

Treatment (retinoid 9cUAB30)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Drug: Retinoid 9cUAB30; Procedure: Therapeutic Conventional Surgery

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (retinoid 9cUAB30)

Retinoid 9cUAB30 DRUG

Given PO

Also known as: (9Z)-UAB-30, 9cUAB30, UAB-30

Treatment (retinoid 9cUAB30)

Therapeutic Conventional Surgery PROCEDURE

Undergo tumor resection surgery

Treatment (retinoid 9cUAB30)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 36228112 DERIVED

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

Specimen Handling; UAB 30

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Results Point of Contact

• Title: Lisa Barroilhet, MD, MS
• Organization: University of Wisconsin - Madison

barroilhet@wisc.edu

608-264-3204

Study Officials

• Helen Krontiras

  University of Wisconsin, Madison

  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: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: August 24, 2016
• Study Start: March 16, 2018
• Primary Completion: June 3, 2022
• Study Completion: June 3, 2022
• Last Updated: June 18, 2024
• Results First Posted: May 22, 2024

Record last verified: 2023-12

Locations

US (5)