Clinical Utility of FES F18 PET/CT in Metastatic Breast Cancer Patients

Study Overview
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Brief Summary
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This is a phase 4, multi-center, open-label, prospective cohort study to evaluate the clinical utility of Fluoroestradiol F18 (Cerianna) PET/CT to guide therapeutic management in ER-positive, HER2-negative metastatic breast cancer patients with progressive disease on first-line standard-of-care hormonal therapy. All patients will undergo a Cerianna PET/CT scan. The treating physician will complete a standardized questionnaire to indicate the second-line therapeutic management plan before the scheduled Cerianna PET/CT. After interpretation of Cerianna PET/CT by local radiologist or nuclear medicine physician, the treating physician will fill out a similar questionnaire to specify the final therapeutic decision. The proportion of patients with a change in therapeutic management plan based on Cerianna PET/CT results will be the primary endpoint. During the study follow-up period of 18 months, data on standard-of-care imaging, treatments/procedures received, and clinical outcomes will be collected. Patients will be asked to complete a health-related quality of life questionnaire at their screening, 6-month, and 18-month visit. Secondary endpoints include visual and quantitative heterogeneity assessment of tumor Cerianna uptake, and PFS rates at 6 months and 18 months after Cerianna PET/CT, which will be assessed between patients with and without a change in therapeutic management plan. Maximum duration of follow-up for each patient: 20 months. First patient first visit to last patient last visit: estimated 36 months.

Official Title
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Clinical Utility of Fluoroestradiol F18 PET/CT in Metastatic Breast Cancer Patients With ER-Positive and HER2-Negative Primary Lesions After Progression on First Line Hormonal Therapy

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: 18F Fluoroestradiol Radiopharmaceutical with PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must sign informed consent prior to enrollment in this trial The patient is a female ≥18 years old Post-menopausal or pre-menopausal patient with known primary breast tumor(s) expressing ER in ≥1% of tumor cells by IHC HER2-negative (0, 1+, 2+ fluorescence in situ hybridization (FISH) negative) primary lesion MBC with at least 1 identifiable lesion on standard-of-care imaging assessment, outside of the liver, as confirmed by the investigator site Patient with progressive disease on 1st line hormonal therapy (Aromatase Inhibitor) with or without a CDK4/6 inhibitor or mechanistic target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinases (PI3K) inhibitor Patient must score at least 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Life expectancy of at least 12 months The patient is planned to undergo a standard-of-care imaging scan (according to National Comprehensive Cancer Network guidelines, e.g., CT and/or bone scan, or fluorodeoxyglucose [FDG]-PET/CT) covering chest, abdomen, and pelvis after date of consent and before Cerianna PET/CT (Visit 2), or the patient has undergone recent standard-of-care imaging before date of consent and is planned to undergo Cerianna PET/CT (Visit 2) no more than 45 days from the standard-of-care imaging scan Exclusion Criteria: Isolated hepatic metastases (taking into account the physiological hepatic high uptake of Cerianna) Patient is on tamoxifen/toremifene treatment without 8-week washout, or on fulvestrant treatment without 28-week washout, (may block ER) before Cerianna PET/CT Other evolutive malignant disease (non-melanoma skin cancer is allowed) or acute or chronic infectious disease (well-controlled infectious disease is allowed); Patient has a history of administered chemotherapy for metastatic disease; prior chemotherapy in the (neo)adjuvant setting is allowed Patient with a known allergy to any of the components of Cerianna Woman of childbearing age who is not using effective contraception Pregnant woman (per the Product Label and ensured using clinic's standard-of-care), or parturient or nursing mother Patient presents with any other clinically active, serious, life-threatening disease, medical, or psychiatric condition, and/or who has a life expectancy of <12 months, or for whom study participation may compromise their management; and/or a patient who the investigator judges to be unsuitable for participation in the study for any reason Inability to comply with any requirements of the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 18F Fluoroestradiol Radiopharmaceutical with PET/CT|Administration of one dose of 18F FES for PET/CT imaging|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate change in therapeutic management plan assessed by comparing pre/post-Cerianna PET/CT treatment selection (based on comparison of the initial management plan and post-Cerianna PET/CT management plan evaluated within 3 weeks). | The percentage of subjects with changes in the therapeutic management plan after Cerianna PET/CT with 95% confidence interval will be estimated by comparison of the initial management plan vs. the post-Cerianna PET/CT management plan evaluated within 3 weeks after Cerianna PET/CT. | [Time Frame: Baseline and within 3 weeks after Cerianna PET/CT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of lesions detected with Cerianna PET/CT (focal Cerianna uptake, outside the liver, visible above background) in individual patients. | Cerianna-uptake score per patient, defined as total number of Cerianna-positive lesions divided by all lesions visible on standard-of-care imaging (e.g., CT and/or bone scan, or FDG-PET/CT) and Cerianna PET/CT (lower scores represent greater ER heterogeneity/ER loss; 0 = a negative scan) | Time Frame: Baseline, Cerianna PET/CT | 
| SUV | Standard uptake values (SUVs, incl. SUVmax, SUVmean, SUVpeak) of each measurable lesion on Cerianna PET/CT and the inter-lesion variability of Cerianna uptake in individual patients | Time Frame: Baseline, Cerianna PET/CT | 
| Heterogeneity | Association between Cerianna heterogeneity scores (inter-lesion SUV variability and Cerianna-uptake score) and patients with/without change in therapeutic management plan | Time Frame: baseline Cerianna PET/CT and within 3 weeks after Cerianna PET/CT | 
| Confidence | Treating physician's confidence level in the therapeutic management plan (measured on a 10-point scale) and the percent change in confidence level before and after Cerianna PET/CT | Time Frame: baseline and within 3 weeks after Cerianna PET/CT | 
| Change in management | Proportion of patients with a change in actual therapeutic management assessed by comparing the therapeutic management plans to the actual therapeutic management at 6 months and 18 months after Cerianna PET/CT | Timeframe: baseline, 6 months and 18 months after Cerianna PET/CT | 
| PFS | PFS rate at 6 and 18 months based on heterogeneity in tumor Cerianna uptake. Comparison will be made between patients with and without a change in therapeutic management plan | Timeframe: baseline, 6 months and 18 months after Cerianna PET/CT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FES, Metastatic breast cancer, PET/CT, Cerianna, Fluoroestradiol F-18