Correlation of 16α-[18F]Fluoro-17β-estradiol PET Imaging With ESR1 Mutation (breast)

Correlation of 16α-[18F]Fluoro-17β-estradiol PET Imaging With ESR1 Mutation for Prognosis Prediction and Response Evaluation of Hormone Therapy in Primary and Metastatic Breast Cancer

The propose of this prospective study focuses on the role of [18F]FES PET imaging in patients with breast cancer who might receive or are receiving hormone therapy. First, we will develop and optimize the radiosynthesis and quality control tests of [18F]FES in conditions that meet good manufacturing practice (GMP) requirements. Secondly, patients with or without metastatic breast cancer will be enrolled for the conduction of human study. [18F]FES PET imaging will be performed on patients before the initiation of hormone therapy to predict the prognosis and therapeutic response to hormone therapy. The [18F]FES PET results will be compared with ER status obtained by immunohistochemical (IHC) staining on surgically obtained specimens. Moreover, in patients with progression of metastatic disease, the [18F]FES PET will be correlated with ESR1 gene mutation, which is one of the mechanisms for resistance to hormone therapy.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 18F-FES PET

Detailed Description

Breast cancer is the fourth leading cancer death both in female and general population in Taiwan. Breast cancer is a cancer with heterogeneous subtypes, based on gene expression profiles and clinicopathological characteristics. Estrogen receptors (ER) expression of breast cancer has significant prognostic values and determines candidate patients for hormone therapy in both adjuvant and metastatic situations. However, ER expression may be variable within the regions of the tumor or discordant between primary and metastatic lesions. Furthermore, ER expression can change over time along the progression of the disease. Many patients receiving hormone therapy finally develop resistance to hormone therapy despite of ER positive result on prior pathologic specimens. Recently, the mutation of ER-related gene ESR1 has been reported to be associated with the mechanism of development of endocrine resistance.

To assist breast cancer treatment, accurate method for patient selection and response prediction to endocrine and other targeted therapy are required. 16α-[18F]fluoro-17β-estradiol ([18F]FES) is currently the only ER-targeted PET agent validated in previous clinical trials. With the development of [18F]FES PET imaging, the status of ER expression could be detected ER status of tumor cell in vivo without the need of an invasive biopsies.

The propose of this prospective study focuses on the role of [18F]FES PET imaging in patients with breast cancer who might receive or are receiving hormone therapy. First, we will develop and optimize the radiosynthesis and quality control tests of [18F]FES in conditions that meet good manufacturing practice (GMP) requirements. Secondly, patients with or without metastatic breast cancer will be enrolled for the conduction of human study. [18F]FES PET imaging will be performed on patients before the initiation of hormone therapy to predict the prognosis and therapeutic response to hormone therapy. The [18F]FES PET results will be compared with ER status obtained by immunohistochemical (IHC) staining on surgically obtained specimens. Moreover, in patients with progression of metastatic disease, the [18F]FES PET will be correlated with ESR1 gene mutation, which is one of the mechanisms for resistance to hormone therapy.

[18F]FES PET is proposed to be served as an interval assessment tool to evaluate the dynamic changes of ER status in patients receiving hormone therapy. Also, the results of this study will demonstrate the impact of [18F]FES PET as a non-invasive tool on decision making of hormone therapy of breast cancer in addition to IHC stain and ESR1 mutation genetic test. After finishing this project, the non-invasive [18F]FES PET imaging will be proved the potential for the improvement of personalized cancer care.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan Univeristy Hospital
    • Contact: Yen Ruoh Fang, MD, PhD; Phone Number: 65581 886223123456; Email: rfyen@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female patients more than twenty years old
• Patients with breast cancer proven by pathology or cytology
• ER status evaluated by immunohistochemical (IHC) staining; Her2 status evaluated by IHC or in-situ hybridization (ISH)
• Patients will receive hormone therapy as adjuvant therapy or treatment of metastatic disease
• Patients with ESR1 gene analysis
• Life expectancy >3 months.
• ECOG performance status 0 to 2

• Hematologic Function：

  1. Neutrophil count ≥1.5×109/L
  2. Platelet count ≥100×109/L
  3. Hemoglobin ≥9.0 g/dL

• Liver Function：

  1. Total bilirubin level ≤ 1.5 mg/dL
  2. Aspartate transaminase (AST) ≤ 77.5 U/L
  3. alanine transaminase (ALT) ≤ 102.5 U/L
  4. (1) Albumin > 25 g/dL
• Renal Function：Creatinine ≤ 2.0 mg/dL

Exclusion Criteria:

• Patients with known secondary malignancy other than breast cancer
• Patients not suitable for hormone therapy after clinical assessment
• Patients who received neoadjuvant chemotherapy, radiation or hormone therapy before the operation of newly diagnosed breast cancer
• Patients treated with oral or intravenous cytotoxic agent(s) during the same period of hormone therapy
• Pregnant or planning pregnant woman
• Unclear consciousness
• Allergy to drug
• Cannot accept 18F-FES PET
• Breastfeeding
• There are other tumors
• By doctor evaluation to unsuitable

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: 18F-FES PET; PET/CT

Drug: 18F-FES PET; 18F-FES PET will be performed for each patient. All patients will receive intravenously injection of 5-8 mCi (185-296 MBq) of 18F-FES. PET imaging will be performed on PET/CT system. The 1-frame dynamic data acquisition of thoracic region including the primary tumor will be started immediately after tracer injection. Whole-body PET acquisition from skull base to upper thigh will be started 60 minutes after tracre injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET imaging	Visual interpretation will be performed first by two independent readers to record if there is any abnormal 18F-FES accumulation. The presence, number, size, character, and location of suspected lesions will be filed for each patient in this study. The final results will be validated by tissue proof, correlation with other imaging, or follow-up results. Semi-quantitative analysis will be performed for each lesion suspected during visual interpretation. Standardized uptake values (SUV) will be obtained by placing regions of interest (ROIs) around the lesions that are identified on visual analysis. The maximum SUV (SUVmax) will be recorded. Volumetric parameters will be performed by placing volume of interests (VOIs) around the suspected lesions. VOIs will be generated using defined fix SUV thresholds or algorithm-generated isocontours. Manual adjustment of VOIs is allowed when non-tumoral tissue is incorrectly included by automatic method.	in 3 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2017
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): June 4, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: breast cancer; PET; estrogen receptor; hormone treatment; [18F]FES; personalized cancer care
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 201512142MINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No