Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02876640
Recruitment Status : Recruiting
First Posted : August 24, 2016
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Early-Stage Breast Carcinoma Invasive Breast Carcinoma Drug: Retinoid 9cUAB30 Procedure: Therapeutic Conventional Surgery Phase 1

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) to 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 TdT-mediated dUTP nick end labeling (TUNEL) 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 activated type I dendritic cells in peripheral blood.

VI. 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.

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

OUTLINE:

Patients receive retinoid 9cUAB30 orally (PO) once daily (QD) for 14 to 28 days. Patients then undergo tumor resection surgery.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Phase Ib 9cUAB30 in Early Stage Breast Cancer to Evaluate Biologic Effect
Actual Study Start Date : March 16, 2018
Estimated Primary Completion Date : February 1, 2022
Estimated Study Completion Date : February 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Treatment (retinoid 9cUAB30)
Patients receive retinoid 9cUAB30 PO QD for 14 to 28 days. Patients then undergo tumor resection surgery.
Drug: Retinoid 9cUAB30
Given PO
Other Name: 9cUAB30

Procedure: Therapeutic Conventional Surgery
Undergo tumor resection surgery




Primary Outcome Measures :
  1. Absolute change in Ki-67 expression in breast epithelial cells of patients treated with 9cUAB30 [ Time Frame: Baseline up to 28 days (post-exposure) ]
    Will be assessed by immunohistochemistry. The baseline, post-exposure, absolute change in Ki-67, and difference in absolute change between the treated and matched controls will all be summarized with descriptive statistics. The primary analysis will compare the difference in absolute change in Ki-67 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.


Secondary Outcome Measures :
  1. Change in apoptosis in breast epithelial cells of patients treated with 9cUAB30 [ Time Frame: Baseline up to 28 days (post-exposure) ]
    Will be assessed by TUNEL assay 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.

  2. Change in gene expression of breast cancer samples using a custom gene panel from Nanostring Technologies [ Time Frame: Baseline up to 28 days (post-exposure) ]
    Change in gene expression will be summarized with descriptive statistics.

  3. Change in maximum concentration (Cmax) [ Time Frame: Baseline up to day 1 ]
    Will be tested by a one-sided one-sample student t-test.

  4. Incidence of observed adverse events [ Time Frame: Up to 28 days ]
    Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Will be compared to know retinoid toxicity. These will be described in descriptive statistics and analyzed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70%
  • Invasive breast cancer between 0.5 cm and 5 cm in size diagnosed by needle core biopsy, estrogen receptor positive (ER+) or estrogen receptor negative (ER-), Her2neu positive or negative
  • 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 within institutional normal limits
  • Fasting triglycerides =< 1.5 x upper limit of normal (ULN)
  • Fasting 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 never used tamoxifen, raloxifene, or other antiestrogen compounds
  • 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) and plasma estradiol 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
  • 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 < 5 years from study entry with the exception of a history of squamous or basal cell carcinoma of the skin < 5 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 TUNEL assays, at a minimum

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02876640


Locations
Layout table for location information
United States, Alabama
University of Alabama at Birmingham Cancer Center Recruiting
Birmingham, Alabama, United States, 35233
Contact: Helen Krontiras    205-934-3028    hkrontir@uabmc.edu   
Principal Investigator: Helen Krontiras         
United States, Iowa
University of Iowa/Holden Comprehensive Cancer Center Not yet recruiting
Iowa City, Iowa, United States, 52242
Contact: Sonia L. Sugg    319-356-7675    sonia-sugg@uiowa.edu   
Principal Investigator: Sonia L. Sugg         
United States, Minnesota
University of Minnesota/Masonic Cancer Center Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Jane Yuet Ching Hui    612-625-2991    jhui@umn.edu   
Principal Investigator: Jane Yuet Ching Hui         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Lee G. Wilke    608-265-5852    wilke@surgery.wisc.edu   
Principal Investigator: Lee G. Wilke         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Helen Krontiras University of Wisconsin, Madison

Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02876640    
Other Study ID Numbers: NCI-2016-01293
NCI-2016-01293 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00033
UW16063 ( Other Identifier: University of Wisconsin Hospital and Clinics )
UWI2015-05-01 ( Other Identifier: DCP )
N01CN00033 ( U.S. NIH Grant/Contract )
P30CA014520 ( U.S. NIH Grant/Contract )
First Posted: August 24, 2016    Key Record Dates
Last Update Posted: November 14, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases