AzTrials
AzTrials

Anatomic Stage I Breast Cancer AJCC v8Phase 1NCT02876640

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

A Phase 1 study testing Biospecimen Collection, Retinoid 9cUAB30 and Therapeutic Conventional Surgery in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage IA Breast Cancer AJCC v8, run by National Cancer Institute (NCI) at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Biospecimen Collection, Retinoid 9cUAB30 and Therapeutic Conventional Surgery
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
5 sitesUnited States
Study dates
16 Mar 2018to 3 Jun 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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 27Show fewer
  • 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

Who cannot join

  • 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,
Show all 17Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Phase Ib 9cUAB30 in Early Stage Breast Cancer to Evaluate Biologic Effect

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Retinoid 9cUAB30, Therapeutic Conventional Surgery
Medical subject headings
Carcinoma, Intraductal, Noninfiltrating

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and urine sample collection

  • Retinoid 9cUAB30Drug

    Also called (9Z)-UAB-30, 9cUAB30, UAB-30

    Given PO

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo tumor resection surgery

Study groups in NCT02876640
Study groupRoleWhat they receive
Treatment (retinoid 9cUAB30)ExperimentalPatients 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.
Receives: Procedure: Biospecimen Collection; Drug: Retinoid 9cUAB30; Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline up to 28 days (post-exposure)

Secondary outcomes (6)

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

    Will be assessed by caspase 3 assays and immunohistochemistry. Change between the treated and matched controls will be summarized with descriptive statistics. Difference in apoptosis will be compared between treatment and matched "control" group using a one-tailed paired t-test or Wilcoxon signed-rank test, as appropriate, at a significance level of 0.05.

    Measured: Baseline up to 28 days (post-exposure)

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

    Change in gene expression will be summarized with descriptive statistics.

    Measured: Baseline up to 28 days (post-exposure)

  3. Change in Maximum Concentration (Cmax)

    Will be tested by a one-sided one-sample student t-test.

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

  4. Incidence of Observed Adverse Events

    Will be graded according to Common Terminology Criteria for Adverse Events version 4.0. Will be compared to know retinoid toxicity. These will be described in descriptive statistics and analyzed.

    Measured: Up to 28 days

  5. Change in Activated Type I Dendritic Cells in Peripheral Blood

    Measured: Baseline up to 28 days (post-exposure)

  6. 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

    Measured: Baseline up to 28 days (post-exposure)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2016 (estimated)
  2. Study start16 Mar 2018
  3. Primary completion3 Jun 2022
  4. Study completion3 Jun 2022

Why it stopped: Inadequate Accrual Rate

Resources

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
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02876640
Sponsor's protocol ID
NCI-2016-01293
Other IDs
NCI-2016-01293, N01-CN-2012-00033, UW16063, UWI2015-05-01, N01CN00033, P30CA014520
Status last verified
Dec 2023
First submitted
19 Aug 2016
Last updated
18 Jun 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36228112

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Retinoid 9cUAB30 and Therapeutic Conventional Surgery in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage IA Breast Cancer AJCC v8, run by National Cancer Institute (NCI) at 5 sites 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 27 inclusion and 17 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: stopped early, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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 22 May 2024). 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?

Absolute Change in Ki-67 Expression in Breast Epithelial Cells of Patients Treated With 9cUAB30 (time frame: Baseline up to 28 days (post-exposure)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02876640, which also lists 1 linked publication.

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 18 Jun 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT02876640 | AzTrials