FES PET/CT in Predicting Response in Patients With Newly Diagnosed Metastatic Breast Cancer Receiving Endocrine Therapy
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|ClinicalTrials.gov Identifier: NCT02398773|
Recruitment Status : Recruiting
First Posted : March 26, 2015
Last Update Posted : August 4, 2020
|Condition or disease||Intervention/treatment||Phase|
|HER2/Neu Negative Progesterone Receptor Negative Progesterone Receptor Positive Stage IV Breast Cancer AJCC v6 and v7||Procedure: Computed Tomography Drug: F-18 16 Alpha-Fluoroestradiol Other: Laboratory Biomarker Analysis Procedure: Positron Emission Tomography||Phase 2|
I. To determine the negative predictive value (NPV) of [18F]fluoroestradiol (FES) uptake for response (clinical benefit) at 6 months in patients with estrogen-receptor positive (ER+) metastatic breast cancer treated with first-line endocrine therapy.
I. To determine the test-retest reproducibility of quantitative assessment of tumor FES uptake by standardized uptake values (SUVs).
II. To evaluate the accuracy of FES-PET/CT for predicting response in patients treated with first line endocrine therapy for metastatic breast cancer.
III. To evaluate the accuracy of FES-PET/CT for predicting progression-free survival (PFS) in patients treated with first line endocrine therapy for metastatic breast cancer.
IV. To examine the role of FES-PET/CT in predicting progressive disease (PD) or clinical benefit (CB), in concert with semi-quantitative interpretation of ER, progesterone receptor (PgR), and marker of proliferation Ki-67 (Ki-67).
V. To evaluate the relationships among FES uptake, as measured by maximum SUV (SUVmax) and semi-quantitative ER from immunohistochemistry (IHC).
VI. To evaluate FES SUVmax < 1.5 as the optimal cutpoint for predicting progression-free survival (PFS) to first line endocrine therapy for metastatic breast cancer.
VII. To determine the percent of eligible patients for whom biopsy is not feasible, i.e., determine the clinical utility of indirect assay of ER expression by FES-PET/CT.
VIII. To evaluate the heterogeneity of tumor FES uptake in individual patients defined as variability in lesion's FES uptake.
Between 0 to 30 days before start of endocrine therapy, patients receive F-18 16 alpha-fluoroestradiol intravenously (IV) over 2 minutes and undergo PET/CT. Patients may undergo a second FES-PET/CT study at least 24 hours after the first study and no later than 10 days after the initial study.
After completion of study, patients are followed up for 6 months and then periodically for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||99 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||[18F] Fluoroestradiol (FES) PET as a Predictive Measure for Endocrine Therapy in Patients With Newly Diagnosed Metastatic Breast Cancer|
|Actual Study Start Date :||February 2, 2016|
|Estimated Primary Completion Date :||April 4, 2022|
Experimental: Diagnostic (FES PET/CT)
Between 0 to 30 days before start of endocrine therapy, patients receive F-18 16 alpha-fluoroestradiol IV over 2 minutes and undergo PET/CT. Patients may undergo a second FES-PET/CT study at least 24 hours after the first study and no later than 10 days after the initial study.
Procedure: Computed Tomography
Drug: F-18 16 Alpha-Fluoroestradiol
Other: Laboratory Biomarker Analysis
Procedure: Positron Emission Tomography
- Negative predictive value of 18F FES uptake for response (CB), defined as the proportion of patients with a negative FES test result who have progressive disease [ Time Frame: At 6 months ]FES-PET results will be assessed as positive or negative by quantitative or qualitative criteria. FES SUVmax < 1.5 will be defined as quantitatively negative test result while one or more sites of active disease will be qualitatively negative test result. The reference standard is patient's tumor response categorized by either CB or PD at 6 months. As part of the preliminary analysis, rates of FES uptake negative results overall and next by tumor response status will be calculated. FES-PET test positive results will be compared in the two tumor response groups using a chi-square test.
- Test-retest reproducibility of quantitative assessment of tumor FES uptake by SUVs [ Time Frame: Up to 6 months ]The reproducibility of the two measurements of SUVs will be assessed by intra-class correlation coefficient and its 95% confidence interval (CI). Additionally, the coefficient of repeatability (CR) and the Bland-Altman plot will be used.
- FES SUVmax [ Time Frame: Up to 6 months ]The receiver operating characteristic (ROC) curve of FES SUVmax and its associated area under an ROC curve (AUC) will be estimated to predict tumor response (clinical benefit). Next, sensitivity and specificity of the dichotomized FES SUVmax (using a cutoff of 1.5) will be estimated non-parametrically, where sensitivity is the proportion of responders having FES SUVmax < 1.5 and specificity is the proportion of non-responders having FES SUVmax > 1.5.
- Predictive accuracy of FES PET/CT for PFS, defined as the time from entry onto study until tumor progression or death from any cause [ Time Frame: Up to 1 year ]To evaluate the predictive accuracy of FES PET, the time-dependent ROC curve of FES SUVmax at pre-specified time points (e.g. 6 months, 1 year) and its corresponding AUC will be estimated. Next, sensitivity and specificity of the dichotomized FES SUVmax (using a cutoff of 1.5) will be estimated in which reference standard is PFS status at pre-specified time points including 6 months and 1 year.
- Significance of FES PET measures in predicting PD or CB, in concert with semi-quantitative interpretation of ER, PgR, and Ki-67 [ Time Frame: Baseline ]Logistic regression analysis will be used to examine the effects of various FES PET measurements on clinical benefit. Predictors are semi-quantitative ER measure, PgR, and Ki-67 based on IHC. Significance of each FES PET measure will be determined by the odds ratio and its 95% CI.
- FES uptake, as measured by SUVmax and semi-quantitative ER from IHC [ Time Frame: Up to 6 months ]The semi-quantitative ER measure will be obtained by using Allred score. The relationship between SUVmax and semi-quantitative ER measure will be evaluated by using a linear regression model treating SUVmax as a dependent variable and semi-quantitative ER measure as a predictor.
- FES SUVmax < 1.5 as the optimal cutpoint for predicting PFS [ Time Frame: Up to 1 year ]Time dependent ROC analysis will be performed to determine the optimal cutoff point for the FES SUVmax and to examine whether there is a more optimal cut-off for dichotomous interpretation of FES SUVmax than the current value 1.5. Specifically, the optimal cut-off point will be determined by maximizing Youden's index for the time dependent ROC curve at a pre-specified time point (e.g. 6 months, 1 year).
- Percent of eligible patients for whom biopsy is not feasible, i.e., clinical utility of indirect assay of ER expression by FES PET [ Time Frame: Up to 6 months ]The proportion of eligible patients for whom biopsy of a metastatic site is not feasible out of a total of 99 patients will be calculated.
- Heterogeneity of tumor FES uptake in individual patients defined as variability in lesion's FES uptake [ Time Frame: Up to 6 months ]Sample correlation matrix for the multiple SUV measurements will be calculated. Next, linear mixed effects model will be used where the outcome is SUV measurements and covariates include fixed effects (sites that the SUV value is measured and patient characteristics). Lesion-specific random effects will be added to the model. The correlations among SUV measurements will be calculated based on the fitted model.
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): NCT02398773
|Principal Investigator:||Farrokh Dehdashti||ECOG-ACRIN Cancer Research Group|