Fluciclovine and PSMA PET/CT for the Classification and Improved Staging of Invasive Lobular Breast Cancer

Phase 1 Feasibility Trial: Improved Staging of Lobular Breast Cancer With Novel Amino Acid Metabolic and Tumor Neovasculature Receptor Imaging

This phase I trial studies how well fluciclovine positron emission tomography (PET)/computed tomography (CT) and PSMA PET/CT work in helping doctors understand and classify invasive lobular breast cancer in patients with invasive lobular breast cancer that is suspicious for or has spread to other places in the body (metastasized). Fluciclovine and PSMA are radiotracers used in PET/CT imaging scans that emit radiation. The PET/CT scan than picks up the radiation being released to create a picture from within the body. Information learned from this study may help researchers learn how to better identify metastatic disease in invasive lobular breast cancer patients which will impact appropriate staging.

Study Overview

• Status: Active, not recruiting
• Conditions: Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Invasive Breast Lobular Carcinoma; Metastatic Breast Lobular Carcinoma
• Intervention / Treatment: Procedure: Computed Tomography; Drug: Gallium Ga 68 Gozetotide; Procedure: Positron Emission Tomography; Drug: Fluciclovine F18

Detailed Description

PRIMARY OBJECTIVES:

I. Improve detection of metastasis with fluciclovine F18 (fluciclovine) and gallium Ga 68-labeled PSMA-11 (PSMA) PET versus best standard of care conventional imaging, as confirmed with histology.

II. Determine concordance and discordance of invasive lobular breast cancer (ILC) detection with PSMA versus fluciclovine PET, as confirmed with histology.

EXPLORATORY OBJECTIVE:

I. Establish the role of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) directed to ESR1 and PI3K DNA in characterizing the degree of tumor burden as identified by metabolic amino acid transport and tumor neovasculature receptor imaging.

OUTLINE:

Patients receive gallium Ga 68-labeled PSMA-11 intravenously (IV) and undergo a PET/computed tomography (CT) scan over 30 minutes. On a separate day, patients receive fluciclovine F18 IV and undergo a PET/CT scan over 30 minutes.

After completion of study, patients are followed up in 5-10 business days, and then up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David Schuster, MD; Phone Number: 404-712-4859; Email: dschust@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Treatment naive biopsy proven ILC patients with ILC
• Either: a) clinical or imaging suspicion of metastatic disease; or b) proven metastatic disease but in whom there is suspicion of an even greater tumor burden that could change therapy approach
• Ability and willingness to undergo biopsy if needed per standard of care for possible metastasis which could change therapy approach

Exclusion Criteria:

• Pregnancy. Qualitative or quantitative serum or urine pregnancy test will be done in women of childbearing potential within 24 hours before PET

  • A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (if age > 55 years); if the female subject is < 55 years and she has been naturally postmenopausal for > 1 year her reproductive status has to be verified by additional lab tests (< 20 estradiol OR estradiol < 40 with follicle-stimulating hormone [FSH] > 40 in women not on estrogen replacement therapy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (Ga PSMA, fluciclovine F18, PET/CT); Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo a PET/CT scan over 30 minutes. On a separate day, patients receive fluciclovine F18 IV and undergo a PET/CT scan over 30 minutes.

Procedure: Computed Tomography; Undergo PET/CT scan; Other Names: CT; CAT; CAT Scan; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Drug: Gallium Ga 68 Gozetotide; Given IV; Other Names: (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC; (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; (68Ga)Glu-urea-Lys(Ahx)-HBED-CC; 68Ga-DKFZ-PSMA-11; 68Ga-HBED-CC-PSMA; 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC; 68Ga-PSMA; 68Ga-PSMA-11; 68Ga-PSMA-HBED-CC; [68Ga] Prostate-specific Membrane Antigen 11; [68Ga]GaPSMA-11; Ga PSMA; Ga-68 labeled DKFZ-PSMA-11; Ga-68 labeled PSMA-11; GA-68 PSMA-11; Gallium Ga 68 PSMA-11; Gallium Ga 68-labeled PSMA-11; GALLIUM GA-68 GOZETOTIDE; Gallium-68 PSMA; Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC; GaPSMA; PSMA-HBED-CC GA-68; Procedure: Positron Emission Tomography; Undergo PET/CT scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; Drug: Fluciclovine F18; Given IV; Other Names: (18F)Fluciclovine; (18F)GE-148; 18F-Fluciclovine; [18F]FACBC; Anti-(18f)FABC; Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid; Anti-[18F] FACBC; Axumin; Fluciclovine (18F); FLUCICLOVINE F-18; GE-148 (18F); GE-148 F-18

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verified detection rate for metastasis	Detection rates are compared between fluciclovine positron emission tomography (PET) and conventional imaging. Paired detection rates will be assessed using McNemar's test. Detection rates will be reported for each method, and 95% confidence intervals will be estimated using the Clopper-Pearson approach. Rates of concordant/discordant observations will be reported.	Up to 5 years
Verified detection rate for invasive lobular breast cancer	Compared between gallium Ga 68-labeled PSMA-11 PET, fluciclovine PET, and conventional imaging. Paired detection rates will be assessed using McNemar's test. Detection rates will be reported for each method, and 95% confidence intervals will be estimated using the Clopper-Pearson approach. Rates of concordant/discordant observations will be reported.	Up to 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of metastasis	Will correlate circulating tumor deoxyribonucleic acid (ctDNA) results with the presence or absence of metastasis. ctDNA parameters will be summarized descriptively using mean, median, minimum/maximum, interquartile range, and standard deviation. ctDNA will be correlated with positron emission tomography uptake parameters using Pearson's or Spearman's correlation coefficient (where appropriate), as well as chi-squared tests, Fisher's exact tests, or analysis of variance if any variables are further categorized	Up to 5 years
Imaging results	Will correlate ctDNA results with the results of imaging.	Up to 5 years

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: David M Schuster, MD, Emory University Hospital/Winship Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Carcinoma; Carcinoma, Lobular; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Anticoagulants; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Edetic Acid; Gallium 68 PSMA-11
• Other Study ID Numbers: STUDY00000675; P30CA138292 (U.S. NIH Grant/Contract); NCI-2020-00366 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); WINSHIP4933-19 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No