The aim of this study is to quantify residual ER binding sites during fulvestrant therapy, compared to the tracer uptake prior to fulvestrant therapy.
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Absolute and relative changes in tracer uptake values during fulvestrant
therapy (after 1 month and 3 months) compared to tracer uptake prior to
fulvestrant therapy.
Secondary outcome
Correlation between tumor response and absolute and relative changes in tracer
uptake
Background summary
Estrogen receptor (ER) positive metastatic breast cancer patients are often
treated with antihormonal therapy. Fulvestrant is an ER-antagonist that
irrversibly blocks the ER and downregulates its expression level. A
dose-response has been shown for fulvestrant's effects on the ER, whereby the
current dose does not yet fully downregulate ER expression. Given the fact that
the current standard dose is generally well tolerated, dose-escalation may be
possible in the near future. Ideally, a biomarker should be available to
evaluate the effects of fulvestrant on the ER to select patients that may
benefit from dose-escalation or increasing the dose frequency. The standard
test to evaluate the ER expression is by immunohistochemistry which can be
performed on biopsies tissue. However, it is not always easy to obtain a biopsy
due to accessibility or risks for complications and furthermore a biopsy only
gives information about a single lesion and may not be representative for the
ER expression in other metastases.
Molecular imaging of the ER with radioactive labeled estrogen (FES) can be used
to quantify ER expression. The aim of this study is to quantify residual ER
binding sites during fulvestrant therapy, compared to the tracer uptake prior
to fulvestrant therapy. Imaging of ER binding sites may be used to optimize
individual patient dosing in the future.
Study objective
The aim of this study is to quantify residual ER binding sites during
fulvestrant therapy, compared to the tracer uptake prior to fulvestrant
therapy.
Study design
In this study we will observe the influence of fulvestrant (a commonly used
estrogen receptor antagonist) on the uptake of radioactive-labeled estradiol by
estrogen receptor positive tumors. Tracer uptake will be evaluated prior to the
start with antihormonal therapy, and during antihormonal therapy.
Study burden and risks
The radiation burden will be approximately 13.2 mSv
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
1. Patients with a history of histological proven ER-positive primary breast cancer and, whenever available, histological proven ER-positive recurrence.
2. Post-menopausal status (age >= 45 years with amenorrhea for > 12 months [with or without concomitant use of LHRH-/GNRH-agonists]or prior bilateral ovariectomy
3. Documentation of a negative pregnancy test must be available for women less than 2 years after menopause
4. Progressive disease after 2 lines of hormonal therapy
5. No previous fulvestrant treatment
6. ER-antagonists should be discontinued for 5 weeks prior to FES-PET to prevent false negative FES_PET results, the use of aromatase inhibitors prior to FES-PET is allowed.
7. At least one measurable lesion according to RECIST v1.1 that is localized outside of the liver
8. ECOG performance status 0, 1 or 2
9. Life expectancy > 3 months
10. Creatinine clearance >= 30 ml/min
11. Age >= 18 years
12. Signed written informed consent
13. Able to comply with the protocol
Exclusion criteria
1. Evidence of central nervous system metastases
2. Presence of life-threatening visceral metastases
3. > 3 lines of endocrine therapy for metastatic disease
4. > 2 lines of chemotherapy in metastatic disease
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-023987-41-NL |
| ClinicalTrials.gov | NCT01377324 |
| CCMO | NL34770.042.10 |