Hybrid Molecular Imaging of ER in Breast Cancer Patients With DCIS

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Вход / Регистрация

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Състояние

Спонсори

University of Wisconsin, Madison

Сътрудници

National Cancer Institute (NCI)

КЛИНИЧНО ИЗСЛЕДВАНЕ: NCT03703492

BioSeek: nct03703492

Ключови думи

Резюме

This prospective, one-arm study which will enroll participants with biopsy-proven DCIS scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care. Eligible participants will be consented for participation in the research study which includes a directed breast PET/MRI with 18F-FES. 18F-FES uptake of the known malignancy will be measured on the PET/MRI examination using standardized uptake values (SUV) and tumor-to-normal tissue ratios.

Описание

Integrated whole-body magnetic resonance imaging (MRI)-positron emission tomography (PET) scanners have recently been introduced for clinical use. This technology combines the anatomic and perfusion data obtained with Dynamic Contrast Enhanced (DCE) MRI with functional imaging data obtained from PET. For breast imaging, the combination of MRI and PET has important potential to improve diagnostic accuracy and provide molecular characterization of breast cancer. The overall purpose of this research is to assess the analytic validity of simultaneous breast DCE MRI with 18F-FES PET for measuring estrogen receptor (ER) in patients with ductal carcinoma in situ (DCIS) and identifying patients with low-risk of disease recurrence. The hypothesis is that quantitative 18F-FES uptake parameters from PET/MRI will correlate well with the ER immunohistochemistry score and with low-risk recurrence scores.

Primary Objective

1) To compare quantitative 18F-FES uptake of biopsy-proven DCIS measured using PET/MRI with ER protein levels determined by immunohistochemistry.

Secondary Objectives

1. To determine the optimal cut-point 18F-FES uptake value for distinguishing between ER+ and ER-negative DCIS

2. To determine the test-retest reproducibility of quantitative assessment of tumor 18F-FES uptake

3. To determine the optimal cut-point 18F-FES uptake value for distinguishing between low-risk DCIS and intermediate/high-risk DCIS

4. To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100)

5. To measure the upgrade rate to invasive cancer at surgical excision

6. To correlate tumor 18F-FES uptake with serum estradiol and sex hormone binding globulin levels.

Дати

Последна проверка:	11/30/2019
Първо изпратено:	10/08/2018
Очаквано записване подадено:	10/08/2018
Първо публикувано:	10/11/2018
Изпратена последна актуализация:	04/01/2020
Последна актуализация публикувана:	04/05/2020
Действителна начална дата на проучването:	01/02/2019
Приблизителна дата на първично завършване:	12/30/2021
Очаквана дата на завършване на проучването:	12/30/2021

Състояние или заболяване

Breast Cancer

Ductal Carcinoma in Situ - Category

Интервенция / лечение

Drug: Research Arm

Фаза

Фаза 2

Групи за ръце

Arm	Интервенция / лечение
Experimental: Research Arm Directed breast PET/MRI with 18F-FES; 18F-FES uptake of the known malignancy to be measured on the PET/MRI examination	Drug: Research Arm 18F-FES is an investigational new drug which will be used for this study. For complete information, please refer to the Investigator's Brochure: "[18F]Fluoroestradiol: An investigational positron emission tomography (PET) radiopharmaceutical for injection, intended for use as an in vivo diagnostic for imaging estrogen receptors in tumors

Критерии за допустимост

Възрасти, отговарящи на условията за проучване	18 Years Да се 18 Years
Полове, допустими за проучване	Female
Приема здрави доброволци	Да
Критерии	Inclusion Criteria: - Diagnosis of biopsy-proven DCIS without invasion or microinvasion measuring at least 1.0 cm in diameter by any imaging modality - Undergoing diagnostic breast MRI ordered by the referring clinician for staging and extent of disease Exclusion Criteria: - Inability or unwillingness to provide informed consent to the study - Surgery, radiation, neoadjuvant chemo/endocrine therapy for the current malignancy prior to study enrollment - Participants currently taking or have taken an ER-blocking medication (e.g. tamoxifen, raloxifene) within 6 weeks prior to study enrollment - Pregnant or lactating women - Participant with intolerance or contraindications for MRI or gadolinium-based contrast agents - Participant girth exceeds the bore of the MRI/PET scanner - Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FES - Participants in liver failure as judged by the patient's physician, due to the hepatobiliary clearance of 18F-FES - Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be allowed to participate as long as the following criteria are met: - The participant has their own prescription for the medication - The informed consent process is conducted prior to the self-administration of this medication - They come to the research visit with a driver or an alternative plan for transportation (e.g. Uber, taxi, etc.)

Резултат

Първични изходни мерки

1. 18F-FES uptake in DCIS [36 months]

18F-FES uptake of biopsy-proven DCIS measured using PET/MRI will be reported in Standardized Uptake Values (SUV).

2. ER immunohistochemistry score [36 months]

The reference standard ER expression will be measured with immunohistochemistry per standard of care and calculated using Allred scoring methods. The Allred score is the sum of the proportion of positive staining tumor cells (scored 0-5 for no stain, <1%, 1-10%, 10-33%, 33-66%, 66-100%, respectively) and the intensity of staining (scored 0-3 for no stain, weak, intermediate, strong, respectively). ER-negative cancers can have either an Allred score of 0 or 2 (1+1). ER-positive cancers can have an Allred score of 3, 4, 5, 6, 7, or 8. An Allred score of 1 does not exist.

3. Correlation of 18F-FES uptake in DCIS to ER immunohistochemistry score [36 months]

The correlation of the two measures will be evaluated with Pearson's correlation coefficient. The null hypothesis is H0: p0=0.50 and the alternative hypothesis is H1: p1 =0.80.

Вторични изходни мерки

1. 18F-FES uptake value for distinguishing between ER+ and ER-negative DCIS [36 months]

Receiver operating characteristic (ROC) curve analysis will be performed to determine the optimal cut-point for 18F-FES uptake to distinguish ER+ from ER-negative DCIS, as defined by the clinical pathology report. The area under the curve (AUC) for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the 18F-FES uptake value with the maximum sensitivity and specificity.

2. Test-retest reproducibility of quantitative assessment of tumor 18F-FES uptake [36 months]

The reproducibility of the two measurements (test-retest) of 18F-FES uptake in the 5 subjects who elect to undergo a second imaging session will be assessed by intra-class correlation coefficient (ICC) and its 95% confidence interval. Additionally, the coefficient of repeatability (CR) and the Bland-Altman plot will be used.

3. Optimal cut-point 18F-FES uptake value for distinguishing between low-risk DCIS and intermediate/high-risk DCIS [36 months]

ROC curve analysis will be performed to determine the optimal cut-point for 18F-FES SUVmax to distinguish low-risk DCIS and intermediate/high-risk DCIS. Risk categories will be determined using the Van Nuys Prognostic Index, the Memorial Sloan-Kettering Cancer Center Nomogram, and the research-based Oncotype DX DCIS score. Sensitivity and specificity will be determined with two-sided 95% confidence intervals. The AUCs for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the 18F-FES uptake value with the maximum sensitivity and specificity. This analysis will be done separately for each risk assessment model.

4. Estimate the association of quantitative 18F-FES uptake with research-based Oncotype DX DCIS scores [36 months]

To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100), scatter plots of continuous quantitative 18F-FES uptake (SUVmax) on the y-axis and research-based Oncotype DX DCIS scores (unitless) on the x-axis will be created to explore the distribution of the measurements. Pearson's or Spearman's rank correlation will be used to evaluate the association between quantitative 18F-FES uptake and research-based Oncotype DX DCIS score. The correlation coefficient (rho) and 95% confidence interval will be reported.

5. Upgrade Rate to Invasive Cancer at Surgical Excision. [36 months]

This percentage will be calculated by dividing the number of patients with invasive breast cancer diagnosed at the time of surgical excision by the number of patients with percutaneous biopsy-proven DCIS in the study.

6. Correlation of Tumor 18F-FES uptake with Serum Estradiol Levels [36 months]

A correlation analysis of serum estradiol levels will be performed using Pearson's or Spearman's rank correlation. Scatter plots, correlation coefficients (rho) and 95% confidence intervals will be reported.

7. Correlation of Tumor 18F-FES uptake with Sex Hormone Binding Globulin Levels [36 months]

A correlation analysis of sex hormone binding globulin levels will be performed using Pearson's or Spearman's rank correlation. Scatter plots, correlation coefficients (rho) and 95% confidence intervals will be reported.

Други изходни мерки

1. Genomic Risk Scores [36 months]

Genomic-based risk scores will be calculated using the Oncotype DX DCIS test. The risk score (0-100) is generated from expression levels of seven cancer related genes and five reference genes determined from a patient's biopsy or surgical specimen. Scores will be categorized and reported as low-risk (0-38), intermediate-risk (39-54), and high-risk (55-100).