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

  • STATUS
    Recruiting
  • End date
    Dec 1, 2022
  • participants needed
    41
  • sponsor
    National Cancer Institute (NCI)
Updated on 17 June 2022
vasectomy
cancer
tubal ligation
hysterectomy
estrogen
breast cancer
fasting
oophorectomy
carcinoma in situ
tamoxifen
estrogen receptor
invasive breast cancer
therapeutic conventional surgery
breast cancer staging
mammogram
core needle biopsy
cancer prevention
raloxifene
breast cancer stage
retinoid 9cuab30

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.

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.

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

Details
Condition 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, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8
Treatment laboratory biomarker analysis, therapeutic conventional surgery, Retinoid 9cUAB30
Clinical Study IdentifierNCT02876640
SponsorNational Cancer Institute (NCI)
Last Modified on17 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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
Prior hysterectomy
one of the following criteria is met
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
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
Psychiatric illness/social situations that will limit compliance with study
requirements
Participant with history of ipsilateral breast radiation
Participant who is breastfeeding or planning to breastfeed for a month post last dose
of study agent
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'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
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