Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Carcinoma in Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Adenocarcinoma

Breast Carcinoma In Situ

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.

Undergo blood and urine sample collection

Biospecimen Collection

Retinoid 9cUAB30

Therapeutic Conventional Surgery

Helen Krontiras

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.

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. 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.

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

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

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

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.

Change in gene expression will be summarized with descriptive statistics.

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

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.

National Cancer Institute (NCI)

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.

Biospecimen Collection: Undergo blood and urine sample collection

Retinoid 9cUAB30: Given PO

Therapeutic Conventional Surgery: Undergo tumor resection surgery

Treatment (Retinoid 9cUAB30)

<18 years

18-64 years

>=65 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Body Mass Index

Respirations

Menopausal Status

Time from Diagnosis to study Entry

Breast Cancer Location

Breast Cancer Biology

Estrogen Receptor Status

HER2 IHC reporting came from the initial diagnostic biopsy. This is a clinical datapoint with no variation of severity. IHC 0 or 1 indicate HER2-negative. IHC 2 is equivocal. IHC 3 indicates HER2- positive.

3 of the cancers were estrogen receptor negative

HER2 IHC Result

This is a results obtained from the clinical pathology report from the participants' initial biopsy. The method of assessment is based on clinical pathological analysis.

Estrogen Receptor Score

This is a result obtained from the clinical pathology report from the participants initial biopsy. The method of assessment is based on clinical pathological analysis.

HER2 FISH

Lisa Barroilhet, MD, MS

One participant's sample did not have any tumor tissue to be analyzed

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

One participant's sample did not have any tumor tissue to analyze

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

Up regulated IL6 expression

Down regulated CDKN2A expression

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

Change in Maximum Concentration (Cmax)

Incidence of Observed Adverse Events

type 1 CD40+mDCs

CD86+ mDCs

type 1 CD86+ macrophages

HLADR+ pDCs

CD33+CD11b+HLA DR+ CD40+ cells

19 patients had matched pre and post samples

Change in Activated Type I Dendritic Cells in Peripheral Blood

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

Overall Study

Participants receive retinoid 9cUAB30 PO QD on days 1 and 8-36. Treatment continues in the absence of unacceptable toxicity.

Participants receive a placebo PO QD on days 1 and 8-36.

Laboratory Biomarker Analysis

Pharmacological Study

Placebo

Jill Kolesar

This randomized phase I trial studies the side effects and best dose of retinoid 9cUAB30 in preventing cancer in healthy volunteers. The use of retinoid 9cUAB30 may keep cancer from forming in healthy volunteers.

PRIMARY OBJECTIVES:

I. To determine the toxicities and recommended phase II dose of 9cUAB30 (retinoid 9cUAB30).

II. To characterize the urine and plasma single dose and steady state pharmacokinetics of 9cUAB30 in normal volunteers.

SECONDARY OBJECTIVES:

I. To correlate the pharmacokinetics of 9cUAB30 with toxicity. II. To compare observed toxicity between placebo controls and each dose level. III. To assess for any change in single dose pharmacokinetics (PK) after repeat dosing (day 1 vs. day 36).

OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.

ARM I: Participants receive retinoid 9cUAB30 orally (PO) once daily (QD) on days 1 and 8-36. Treatment continues in the absence of unacceptable toxicity.

ARM II: Participants receive a placebo PO QD on days 1 and 8-36.

After completion of study treatment, patients are followed up at 7 and 30 days.

Retinoid 9cUAB30 in Preventing Cancer in Healthy Volunteers

A Randomized, Double-Blind, Phase I Dose-Escalation Study of the Novel Retinoid 9cUAB30

Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Basic pharmacokinetic and summary pharmacokinetic measures from the extensive plasma sampling on days 1 and 36, and levels obtained from single plasma and urine samples taken on days 8, 15, 22, and 29 will be summarized with basic statistics, including means, standard errors, medians, and interquartile ranges by dose, visit, and time point, as available.

The pharmacokinetics of retinoid 9cUAB30 will be compared between day 1 and day 36 using one-sample t-tests, or Wilcoxon signed-rank tests as appropriate in order to evaluate the single vs. steady state levels. An appropriate regression model will be used to explore the relationship of dose with change in PK: logarithmic transformations will be used as necessary.

Patient toxicity will be summarized by the presence or absence of any toxicities, worst CTCAE grade, and strongest investigator defined relationship will all be examined and characterized by dose. Correlations between the different PK measures of retinoid 9cUAB30 and the different measures of toxicity will be estimated with polyserial correlation. To compare toxicities at each dose level to placebo, the Chi-square test will be used for the presence or absence of toxicities, and Wilcoxon rank-sum tests will be used for CTCAE grade and investigator defined relationship data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Retinoid 9cUAB30 in Producing a Biologic Effect in Patients With Early Stage Breast Cancer	NCT02876640	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Breast Ductal C... Early Stage Bre... Invasive Breast...	Biospecimen Col... Retinoid 9cUAB3... Therapeutic Con...	18 Years -	National Cancer Institute (NCI)
Retinoid 9cUAB30 in Preventing Cancer in Healthy Volunteers	NCT01935960	Healthy Subject	Laboratory Biom... Pharmacological... Placebo Retinoid 9cUAB3...	18 Years - 65 Years	National Cancer Institute (NCI)
Retinoid 9cUAB30 in Producing a Biologic Effect in Patients With Early Stage Breast Cancer	NCT02876640	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Breast Ductal C... Early Stage Bre... Invasive Breast...	Biospecimen Col... Retinoid 9cUAB3... Therapeutic Con...	18 Years -	National Cancer Institute (NCI)
Retinoid 9cUAB30 in Producing a Biologic Effect in Patients With Early Stage Breast Cancer	NCT02876640	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Breast Ductal C... Early Stage Bre... Invasive Breast...	Biospecimen Col... Retinoid 9cUAB3... Therapeutic Con...	18 Years -	National Cancer Institute (NCI)

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