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

March 16, 2010
May 20, 2014
February 2010
February 2014   (final data collection date for primary outcome measure)
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.

FES-PET standard uptake value to predict response to estrogen therapy [ Time Frame: Follow up at 1 month, 2 months, 3 months and every 3 months thereafter. FES-PET data will retrospectively be analyzed after responders and non-responders have been defined. ] [ Designated as safety issue: No ]
With a ROC analysis we will determine the optimal sensitivity and specificity of FES-PET in relation with the standard uptake value (SUV) to predict response to estrogen therapy
Complete list of historical versions of study NCT01088477 on ClinicalTrials.gov Archive Site
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Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer
Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer

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.

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.

Observational
Observational Model: Case-Only
Time Perspective: Prospective
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Non-Probability Sample

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

Breast Cancer
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.
Breast cancer patients with acquired anti-hormonal resistance
Intervention: Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
February 2014
February 2014   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01088477
RUG 2009-4529
No
G.A.P. Hospers, University Medical Centre Groningen
University Medical Centre Groningen
Dutch Cancer Society
Not Provided
University Medical Centre Groningen
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP