Retinoid 9cUAB30 in Producing a Biologic Effect in Patients With Early Stage Breast Cancer
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.
- Early-Stage Breast Carcinoma
- Invasive Breast Carcinoma
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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
- 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
- Phase 1
- Study Type
- Intervention Model
- Single Group Assignment
- Primary Purpose
- None (Open Label)
Treatment (retinoid 9cUAB30)
|Patients receive retinoid 9cUAB30 PO QD for 14 to 28 days. Patients then undergo tumor resection surgery.||
- National Cancer Institute (NCI)
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.
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.
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.