Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
G.A.P. Hospers, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01377324
First received: May 19, 2011
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

The dose of fulvestrant to optimally downregulate estrogen receptors (ER) is currently subject of debate. Effects of fulvestrant on the ERs may be evaluable by molecular imaging using positron emission tomography with the ER-specific FES tracer. In this pilot study we will evaluate the effects of the new dose of fulvestrant (500mg i.m.)on the availability of ER binding sites in 15 metastatic breast cancer patients.


Condition Intervention Phase
Metastatic Breast Cancer
Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Visualize and quantify changes in FES uptake in tumor lesions during fulvestrant 500mg therapy [ Time Frame: baseline; 1 month; 3 months ] [ Designated as safety issue: No ]

    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

  • To evaluate the proportion of patients with an incomplete down-regulation/occupancy of ERs as determined by FES-PET [ Time Frame: baseline, 1 month and 3 months ] [ Designated as safety issue: No ]

    FES-uptake will be calculated for all tumor lesions at baseline, after 1 month and after 3 months.

    Incomplete down-regulation/ occupancy of ERs is defined as 1) an absolute SUV> 1.5, and 2) a relative decrease in SUV of <75% during fulvestrant therapy.

    The proportion of patients that match these criteria will be given for:

    • 1 month minus baseline
    • 3 months minus baseline


Secondary Outcome Measures:
  • The feasibility to quantify changes in FES-uptake in liver metastases [ Time Frame: baseline, 1 month and 3 months ] [ Designated as safety issue: No ]
    Liver metastases detected on PET/CT will be serially quantified at the 3 different time points to evaluate the feasibility to quantify liver lesions on FES-PET/CT

  • to correlate FES-PET results to patient and tumor response on fulvestrant therapy [ Time Frame: baseline, 1 month, 3 months ] [ Designated as safety issue: No ]

    Patients will be categorized as responders and non-responders by standard follow-up (monthly visits, 3-monthly CT, other techniques when indicated).

    The predictive value of FES-PET for response to fulvestrant will be calculated for:

    • baseline FES-uptake
    • changes in FES-uptake from baseline to 1 month
    • changes in FES-uptake from baseline to 3 months

    Lesion-based evaluation will be performed for measurable lesions as defined by RECIST criteria, and changes in diameter will be correlated to changes in FES-uptake at:

    • 1 month minus baseline
    • 3 months minus baseline

  • Explorative analysis to correlate several factors (among which tumor burden, ER-expression, fulvestrant levels, estradiol levels, patient weight) to FES uptake will be performed. [ Time Frame: baseline, 1 month and 3 months ] [ Designated as safety issue: No ]
    Explorative analysis to correlate several factors at different timepoints (baseline, 1 month, 3 months) to FES uptake.


Enrollment: 16
Study Start Date: May 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm
Fluoroestradiol-PET is performed at baseline, after 1 month, and 3 months
Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol
A FES-PET/(CT) will be performed thrice during protocol execution. Patients will be injected with ~200MBq 18F-FES

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01377324

Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713GZ
Sponsors and Collaborators
University Medical Centre Groningen
  More Information

Publications:
Responsible Party: G.A.P. Hospers, MD PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01377324     History of Changes
Other Study ID Numbers: RUG2010-2611
Study First Received: May 19, 2011
Last Updated: October 14, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Centre Groningen:
Breast cancer
Fulvestrant
FES
PET
Positron
Emission
Tomography
Fluoroestradiol
FES-PET
Molecular Imaging
Estrogen Receptor

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014