|- candidate number||7803|
|- NTR Number||NTR2234|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||1-mrt-2010|
|- Secondary IDs||2008.277 METc UMCG|
|- Public Title||Moleculaire beeldvorming van de oestrogeenreceptor dichtheid om de hormonale behandelingsmogelijkheden voor patiŽnten met borstkanker te verbeteren.|
|- Scientific Title||Imaging of ER density to guide and improve tailored therapy for acquired anti-hormonal resistant breast cancer.|
|- hypothesis||Measuring ER-density with FES-PET can be used as a predictive test to select patients sensitive for estrogen therapy.|
|- Healt Condition(s) or Problem(s) studied||Breast cancer, Acquired anti-hormonal resistance|
|- 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.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-feb-2010|
|- planned closingdate||1-feb-2013|
|- Target number of participants||50|
|- Interventions||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 benifit will be used as criteria. In case of disease progression before end of the study period, estradiol treatment will be stopped. |
|- Primary outcome||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. |
|- Secondary outcome||1) To discriminate the acquired anti-hormonal resistant phenotypes in patients based on ER expression levels by FES-PET;|
2) Correlation between SUV and response to therapy.
|- Timepoints||At the start of study ER densitity will be determined by FES-PET, the patient will be staged with CT-scan, and baseline clinical information will be collected (laboratory results, VAS-score, ECOG performance, ECG).|
Follow-up will take place monthly during the first 3 months, and thereafter every 3 months.
|- Trial web site||http://www.medischeoncologiegroningen.nl/D76.php|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD, PhD G.A.P. Hospers|
|- CONTACT for SCIENTIFIC QUERIES||MD, PhD G.A.P. Hospers|
|- Sponsor/Initiator ||University Medical Center Groningen (UMCG), Department of Internal Medicine: Division of Medical Oncology|
(Source(s) of Monetary or Material Support)
|- Publications||1. Dehdashti F, Mortimer JE, Trinkaus K. et al. PET-based estradiol challenge as a predictive biomarker of response to endocrine therapy in women with estrogen-receptor-positive breast cancer. Breast Cancer Res Treat (2009) 113:509-517;|
2. Ellis MJ, Dehdashti F, Kommareddy A et al. A randomized phase 2 trial of low dose (mg daily) versus high dose (30mg daily) estradiol for patients with estrogen receptor positive aromatase inhibitor resistant advanced breast cancer. Breast Cancer Symposium 2008 San Antonio.
|- Brief summary||Patients with different types of acquired anti-hormonal resistance are likely to respond differently to a particular kind of treatment. The ER+ subtype would most likely initially respond to a second or third line of anti-hormonal therapy, but ultimately these tumors will again become resistant. At that stage, chemotherapy is the only treatment available. Chemotherapy is currently also the only treatment option for tumors of the ER- phenotype. In contrast, treatment with estrogen is highly effective for the hypersensitive ER++ phenotype and could therefore be an attractive alternative for chemotherapy in this selected group of patients. Currently, this treatment option is not utilized due to the absence of proper stratification methods.
FES-PET may allow identification of patients without ER expression (ER-), patients with preserved ER expression (ER+) and patients with ER overexpression (ER++). This project therefore aims to investigate in a pilot clinical study whether the acquired anti-hormonal resistant phenotypes in breast cancer patients can be discriminated on basis of ER expression levels as measured by FES-PET. The discrimination of phenotypes could allow selection of patients eligible to estrogen treatment.
|- Main changes (audit trail)|
|- RECORD||1-mrt-2010 - 12-mrt-2010|