18F-Fluoroestradiol-PET/CT Scan for the Detection of Metastatic Disease in Patients with Invasive Breast Lobular Cancer
This phase II trial studies a new positron emission tomography/computed tomography (PET/CT) scan using a radioactive imaging agent called fluoroestradiol F-18 to evaluate whether this method may improve the detection of invasive breast lobular cancer that has spread to other places in the body (metastatic). Radioactive drugs, such as fluoroestradiol F-18, may carry radiation directly to tumor cells and not harm normal cells. Diagnostic procedures such as 18F-Fluoroestradiol-PET/CT, may identify sites of cancer in patients with invasive breast lobular cancer.
Inclusion Criteria
- PILOT PHASE: Adults aged 18 years or greater
- PILOT PHASE: All patients or legal guardians are willing and able to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with local and institutional guidelines
- PILOT PHASE: Histologically confirmed invasive lobular carcinoma within the past 12 weeks confirmed from biopsy of primary tumor or metastasis
- PILOT PHASE: Patient is willing to have their clinical records reviewed for at least 24 months after enrollment
- EXPANSION PHASE: Adults aged 18 years or greater
- EXPANSION PHASE: All patients or legal guardians are willing and able to sign a written informed consent and HIPAA authorization in accordance with local and institutional guidelines
- EXPANSION PHASE: Patient must qualify for one of the following: * Primary endpoint analysis/Primary Arm: ** Histologically confirmed ER+ invasive lobular carcinoma within the past 16 weeks confirmed from biopsy of primary tumor or metastasis (n=40). * Exploratory Arm 1: ** Histologically confirmed ER+ invasive lobular carcinoma at any time in the past, confirmed from biopsy of primary tumor or metastasis, with confirmed or imaging suspected metastatic disease, currently on antihormonal therapy or chemotherapy (n=10). * Exploratory Arm 2: ** Histologically confirmed ER- invasive lobular carcinoma (at any point) at any site with biopsy-proven or imaging suspected metastatic ILC (n=5).
- EXPANSION PHASE: Patient is willing to have their clinical records reviewed, and be contacted by phone during follow-up intervals specified, for approximately 60 months after enrollment
- EXPANSION PHASE: Patient is willing to provide baseline blood specimens for ctDNA analysis
- EXPANSION PHASE: Patients who are too claustrophobic to undergo PET/CT scanning
Exclusion Criteria
- PILOT PHASE: Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
- PILOT PHASE: Patients who require monitored anesthesia for PET/CT scanning
- PILOT PHASE: Patients who are too claustrophobic to undergo PET/CT scanning
- PILOT PHASE: Pregnancy or current breast feeding
- PILOT PHASE: Any patient that is medically unstable defined as a patient requiring inpatient hospitalization or needing evaluation at an acute care or urgent care facility at time of imaging
- PILOT PHASE: Patients undergoing treatment with estrogen receptor agonists (such as fulvestrant and tamoxifen) within 5 weeks of the FES-PET/CT scan. (Note that aromatase inhibitors and luteinizing hormone-releasing hormone agonists do not affect ER expression, or binding of FES to ER, and do not need to be discontinued or considered for inclusion or exclusion of patients)
- PILOT PHASE: Patient who have had the site(s) of biopsy proven invasive lobular carcinoma surgically resected
- EXPANSION PHASE: Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator’s discretion
- EXPANSION PHASE: Patients who require monitored anesthesia for PET/CT scanning
- EXPANSION PHASE: Pregnancy or current breast feeding
- EXPANSION PHASE: Patient who have had the site(s) of biopsy proven invasive lobular carcinoma surgically resected. Note: This does not apply for participants being enrolled for exploratory arm 1
- EXPANSION PHASE: Patients undergoing treatment with estrogen receptor agonists (such as fulvestrant and tamoxifen) within 5 weeks of the FES-PET/CT scan. (Note that aromatase inhibitors and luteinizing hormone releasing hormone agonists do not affect ER expression, or binding of FES to ER, and do not need to be discontinued or considered for inclusion or exclusion of patients). Note: This does not apply for participants being enrolled for exploratory arm 1
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04252859.
PRIMARY OBJECTIVE:
I. To assess the positive detection rate of invasive lobular carcinoma (ILC) on F-18 16 alpha-fluoroestradiol ([18F]fluoroestradiol) PET/CT (fluoroestradiol[FES]-PET/CT). (PILOT PHASE COMPLETED MARCH 2022)
II. To assess change in staging of patients with newly diagnosed ILC (primary study arm, n=40) based on FES-PET/CT results per the American Joint Committee on Cancer (AJCC) TNM staging system. (EXPANSION PHASE)
SECONDARY OBJECTIVES:
I. To assess FES-PET/CT concordance with estrogen receptor (ER) status from biopsy and presence of intertumoral ER heterogeneity. (PILOT PHASE COMPLETED MARCH 2022)
II. To assess for any differences between fludeoxyglucose (FDG)- and FES-PET/CT uptake. (PILOT PHASE COMPLETED MARCH 2022)
III. To assess whether quantity of methylated ctDNA at baseline (primary study arm, n=40) predicts patient stage at presentation per the American Joint Committee on Cancer (AJCC) TNM system. (EXPANSION PHASE)
IV. To assess whether quantity of methylated ctDNA at baseline (primary study arm, n=40) predicts survival at each follow-up interval starting at 6 months (follow-up performed at 6, 12, 18, 24, 36, 48 and 60 months). (EXPANSION PHASE)
V. To assess whether heterogeneous FES-PET/CT uptake at baseline (yes/no) (primary study arm, n=40), defined as abnormal FES uptake in some but not all proven or suspected ILC lesions, predicts survival at each follow-up interval starting at 6 months (follow-up performed at 6, 12, 18, 24, 36, 48 and 60 months). (EXPANSION PHASE)
EXPLORATORY OBJECTIVES: (EXPANSION PHASE)
I. Evaluate rate of complete ER blockade (yes/no) on optional post-therapy FES-PET/CT study (primary arm, n=10 patients) with ER+ ILC completing an optional FES-PET/CT study 2-4 weeks after therapy onset.
II. Evaluate rate of persistent FES uptake (yes/no) on optional FES-PET/CT (exploratory arm 1, n=10) for individuals with known metastatic initially ER positive ILC currently on hormonal therapy.
III. Assess the negative predictive value of FES-PET/CT imaging (exploratory arm 2, n=5) for individuals with estrogen receptor (ER) negative ILC as determined by immunohistochemistry from core needle biopsy.
IV. Assess whether heterogeneous FES-PET/CT uptake at baseline (yes/no) for participants in primary and exploratory arm 2, defined as abnormal FES uptake in some but not all proven or suspected ILC lesions, predicts development of recurrent disease (yes/no) for patients with no distant metastatic disease at baseline, during follow-up starting at 6 months (follow-up performed at 6, 12, 18, 24, 36, 48 and 60 months).
V. To assess whether heterogeneous FES-PET/CT uptake at baseline (yes/no) for participants in all study arms, defined as abnormal FES uptake in some but not all proven or suspected ILC lesions, predicts development of new metastatic disease during follow-up (yes/no) for patients who have metastatic disease at baseline, during follow-up starting at 6 months (follow-up performed at 6, 12, 18, 24, 36, 48 and 60 months).
VI. Assess whether quantity of methylated ctDNA at baseline for participants in primary arm and exploratory arm 2 predicts development of recurrent disease (yes/no) for patients with no distant metastatic disease at baseline, during follow-up starting at 6 months (follow-up performed at 6, 12, 18, 24, 36, 48 and 60 months).
VII. To assess whether quantity of methylated ctDNA at baseline for participants in all study arms predicts development of new metastatic disease during follow-up (yes/no) for patients who have metastatic disease at baseline, during follow-up starting at 6 months (follow-up performed at 6, 12, 18, 24, 36, 48 and 60 months).
OUTLINE:
PILOT PHASE (COMPLETED MARCH 2022) : Patients receive 18-FES intravenously (IV) over 30 seconds, then undergo PET/CT over 61 minutes. Patients may also undergo a 18-FDG-PET/CT scan within 4 weeks before or after the 18-FES-PET/CT scan.
EXPANSION PHASE:
Patients receive 18-FES intravenously (IV) over 30 seconds, then undergo PET/CT over 61 minutes. Patients undergo blood sample collection. Patients may also undergo a 18-FDG-PET/CT scan within 4 weeks before or after the 18-FES-PET/CT scan.
Trial PhasePhase II
Trial Typediagnostic
Lead OrganizationHuntsman Cancer Institute/University of Utah
Principal InvestigatorJeffrey T. Yap
- Primary IDHCI128055
- Secondary IDsNCI-2020-13245
- ClinicalTrials.gov IDNCT04252859