Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Lobular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Adenocarcinoma

All Drugs and Chemicals

Anti-Infective Agents

Anticoagulants

Bone Density Conservation Agents

Amino Acids

Gallium 68 PSMA-11

Carbamide Peroxide

Edetic Acid

Pentetic Acid

Chelating Agents

Calcium

Calcium, Dietary

Radiopharmaceuticals

Lysine

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.

Computed Tomography

Fluciclovine F18

Gallium Ga 68 Gozetotide

Positron Emission Tomography

David M Schuster, MD

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.

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.

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

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

Will correlate ctDNA results with the results of imaging.

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.

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.

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Emory University

Principal Investigator

Neratinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive standard of care endocrine therapy over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.

Patients receive standard of care endocrine therapy and neratinib PO over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then continue endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.

Endocrine Therapy

Biopsy of breast

Biospecimen Collection

Mammogram

Undergo breast Magnetic Resonance Imaging

Magnetic Resonance Imaging

Breast Surgery

Ultrasound

Vanderbilt-Ingram Services for Timely Access

Kevin Kalinsky, MD

Adam Brufsky, MD

Vanderbilt-Ingram Service for Timely Access

Laura Kennedy, MD, PhD

Carlos Arteaga, MD

Bora Lim, MD

This phase II trial tests how well neratinib prior to the primary treatment (neoadjuvant) works in treating patients with stage I-III HER2 mutated lobular breast cancers. Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving neratinib in addition to normal therapy may work better in treating cancer than the endocrine therapy patients would normally receive.

PRIMARY OBJECTIVE:

I. Determine efficacy of neoadjuvant neratinib in combination with endocrine therapy.

SECONDARY OBJECTIVES:

I. Determine additional efficacy outcomes of neoadjuvant neratinib in combination with endocrine therapy.

II. Compare the safety and tolerability of neratinib plus endocrine therapy.

CORRELATIVE OBJECTIVE:

I. Establish HER2-mutant invasive lobular carcinoma (ILC) organoids.

OUTLINE: Patients are randomized to 1 of 2 treatments.

TREATMENT A: Patients receive standard of care endocrine therapy over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then endocrine therapy and neratinib orally (PO) daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast magnetic resonance imaging (MRI) prior to surgery.

TREATMENT B: Patients receive standard of care endocrine therapy and neratinib PO over 4 weeks for 1 cycle. Patients undergo breast tissue biopsy during the lead-in window/cycle 1. Patients then continue endocrine therapy and neratinib PO daily for 20 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo breast surgery during weeks 24-25. Patients undergo collection of blood samples every 4 weeks while on treatment, at weeks 4 and 24, and at time of surgery. Patients undergo mammogram, ultrasound, or breast MRI prior to surgery.

After completion of study treatment, patients are followed up for 4 weeks after study drugs interruption.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fluciclovine and PSMA PET/CT for the Classification and Improved Staging of Invasive Lobular Breast Cancer	NCT04750473	Anatomic Stage ... Invasive Breast... Metastatic Brea... Prognostic Stag...	Computed Tomogr... Fluciclovine F1... Gallium Ga 68 G... Positron Emissi...	18 Years -	Emory University
Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers	NCT05919108	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Invasive Breast...	Endocrine Thera... Biopsy of breas... Neratinib Biospecimen Col... Mammogram Magnetic Resona... Breast Surgery Ultrasound	18 Years -	Vanderbilt-Ingram Cancer Center
Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers	NCT05919108	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Invasive Breast...	Endocrine Thera... Biopsy of breas... Neratinib Biospecimen Col... Mammogram Magnetic Resona... Breast Surgery Ultrasound	18 Years -	Vanderbilt-Ingram Cancer Center

Spots Global Cancer Trial Database for invasive breast lobular carcinoma