In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET
18 Years
N/A
Both
Metastatic Breast Cancer
Trial Information
In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET
The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In
these patients signaling via the ER induces proliferation and cell survival of malignant
cells. Fulvestrant can inhibit this signaling route by blocking the receptor and decreasing
ER-expression by increasing its turn-over rate.
The historical standard dose of fulvestrant was 250mg every 28 days i.m.; however studies
performing serial biopsies showed that ER-downregulation was suboptimal. Recently the
standard dose has been set to 500mg i.m. on day 1; 14; 28 and every 28 days thereafter.
Although slightly more effective than the 250mg dose, still questions remain with respect to
the required dose to establish maximal downregulation of ER-signaling.
Immunohistochemistry only provides static information, i.e. the level of ER-expression.
However, dynamic information evaluating the effects of fulvestrant on occupancy of ERs, may
also be valuable.
Whole-body imaging of the availability of ER binding sites using FES-PET may prove valuable
to evaluate the effects of fulvestrant on the ER non-invasively in individual patients. This
potentially allows adjustment of dosing in individual patients to aid therapy efficacy.
In this pilot-study we will evaluate 15 metastatic breast cancer patients. All patients will
undergo FES-PET/CT at baseline, FES-PET after 1 month, and FES-PET/CT after three months.
Hormone- and fulvestrant levels will be measured in all patients. Whenever possible, tumor
biopsies will be performed to correlate to FES-PET results.
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 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 is allowed 7. ECOG performance status 0, 1 or 2 8.
Life expectancy > 3 months 9. Creatinine clearance ≥ 30 ml/min 10. Age ≥ 18 years 11.
Signed written informed consent 12. 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Outcome Measure:
Visualize and quantify changes in FES uptake in tumor lesions during fulvestrant 500mg therapy
Outcome Description:
FES-uptake will be calculated for all tumor lesions at baseline, 1 month and 3 months. Changes between FES-uptake during fulvestrant therapy will be calculated for: 3 months minus baseline 3 months minus 1 month 1 month minus baseline
Outcome Time Frame:
baseline; 1 month; 3 months
Safety Issue:
No
Authority:
Netherlands: Medical Ethics Review Committee (METC)
Study ID:
RUG2010-2611
NCT ID:
NCT01377324
Start Date:
May 2011
Completion Date:
October 2013
Related Keywords:
- Metastatic Breast Cancer
- Breast cancer
- Fulvestrant
- FES
- PET
- Positron
- Emission
- Tomography
- Fluoroestradiol
- FES-PET
- Molecular Imaging
- Estrogen Receptor
- Breast Neoplasms
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