We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01377324
First Posted: June 21, 2011
Last Update Posted: October 16, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
G.A.P. Hospers, University Medical Centre Groningen
  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: Intervention Model: Single Group Assignment
Masking: None (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 G.A.P. Hospers, 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 ]

    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 ]

    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 ]
    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 ]

    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 ]
    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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01377324


Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713GZ
Sponsors and Collaborators
University Medical Center 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
First Submitted: May 19, 2011
First Posted: June 21, 2011
Last Update Posted: October 16, 2013
Last Verified: October 2013

Keywords provided by G.A.P. Hospers, University Medical Centre Groningen:
Breast cancer
Fulvestrant
FES
PET
Positron
Emission
Tomography
Fluoroestradiol
FES-PET
Molecular Imaging
Estrogen Receptor

Additional relevant MeSH terms:
Estrogens
Estradiol
Polyestradiol phosphate
Fulvestrant
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol valerate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female