Clinical trial NCT03544762: Correlation of 16α-[18F]Fluoro-17β-estradiol PET Imaging With ESR1 Mutation
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: breast cancer
PET
[18F]FES
estrogen receptor
hormone treatment
personalized cancer care
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2018-06-04
Enrollment: 60
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: PET imaging
timeFrame: in 3 days
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan Univeristy Hospital
Study officials:
References: