Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Dutch Cancer Society
Information provided by (Responsible Party):
G.A.P. Hospers, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01088477
First received: March 16, 2010
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

In 50 breast cancer patients, heavily pretreated with anti-hormonal therapy, the investigators will evaluate the use of 16-alpha[18-fluoro]-17beta-estradiol positron emission tomography (FES-PET)as predictive biomarker for response to estrogen therapy.


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

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Quantifying FES-uptake to predict response to estrogen therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    FES-uptake (prior to estrogen therapy) of tumour lesions will be recorded for all patients.

    Patients will be prospectively categorized into responders and non-responders during standard follow-up (consisting of monthly visits, 3-monthly CT, and other techniques when indicated). Patients with complete response, partial response or stable disease for >6 months are defined as 'responders'.

    With ROC analysis we will determine the optimal cut-off value for FES-uptake to predict response to estrogen therapy.



Enrollment: 21
Study Start Date: February 2010
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Breast cancer patients with acquired anti-hormonal resistance Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol
In patients with acquired antihormonal resistance, eligible for estrogen therapy, a FES-PET scan will be made to determine FES-PET tumor uptake (which corresponds to estrogen receptor expression levels). Immediately after the FES-PET scan, all patients will start with a standard accepted dose of 2mg estradiol TID. Therapy response will be monitored by regular follow-up. RECIST criteria and clinical benefit will be used as criteria. In case of disease progression before end of the study period, estradiol treatment will be stopped.

Detailed Description:

The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In general, for these patients anti-hormonal therapy is the therapy of first choice. Despite good responses in 50-60% of the patients, unfortunately all patients develop (acquired) resistance. Patients with acquired anti-hormonal resistance can be subdivided into three different groups: (1) patients that have lost ER-expression (~25%), (2) patients with preserved ER-expression (~55%) and (3) patients with enhanced ER-expression (~30%). Several studies suggest different treatment strategies for these three different ER-phenotypes in antihormonal resistant breast cancer. In patients with acquired anti-hormonal resistance, ~30% of the patients still respond to hormone-additive therapy with estrogens. In vitro studies have shown estrogen-induced apoptosis in long-treated estrogen deprived cells (simulating aromatase inhibitor resistance). It is suggested that this estrogen-hypersensitivity is accompanied by increased ER-expression.

Whole-body imaging of ER-density is now possible with positron emission tomography with the 16-alpha[18-fluoro]-17beta-estradiol tracer (FES-PET). FES-PET has shown to be a predictive biomarker for response to first line anti-hormonal therapy.

In this study we will include 50 patients, heavily pretreated with anti-hormonal therapy. All patients will undergo FES-PET at baseline and start estrogen therapy. Investigators and patients will be blinded for FES-PET results. Responders and non-responders will be defined using RECIST criteria and clinical follow-up. After response has been determined, FES-PET results will be analyzed. We hypothesize that patients responding to estrogen therapy can be identified on basis of high ER-expression determined by FES-PET.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Breast cancer patients with acquired anti-hormonal resistance, treated with at least 2 lines of anti-hormonal therapy

Criteria

Inclusion Criteria:

  1. Patients with the diagnosis of acquired anti-hormonal resistant advanced breast cancer showing progression after two or more lines of antihormonal treatment;
  2. Treatment with estradiol will be started;
  3. Age> 18 years;
  4. ECOG performance status 0-2.

Exclusion Criteria:

  1. Life Expectancy <3 months;
  2. Uncontrolled CNS metastases;
  3. History of thrombosis;
  4. Uncontrolled hypercalcemia;
  5. Treatment with any investigational drug within 30 days before start of study;
  6. Serious uncontrolled concurrent illness, e.g. autoimmune disorders;
  7. New York Hearth Association (NYHA) class III/IV congestive heart failure;
  8. Dyspnea at rest due to any cause;
  9. Pregnant or lactating women. Documentation of a negative pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than two years after menopause;
  10. Women of childbearing potential unless a) surgically sterile or b) using adequate measures of contraception.
  11. Diabetes Mellitus
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01088477

Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700 RB
Sponsors and Collaborators
University Medical Centre Groningen
Dutch Cancer Society
  More Information

Publications:
Responsible Party: G.A.P. Hospers, MD PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01088477     History of Changes
Other Study ID Numbers: RUG 2009-4529
Study First Received: March 16, 2010
Last Updated: May 20, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Centre Groningen:
Acquired anti-hormonal resistant breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 23, 2014