Prevalence of Genetic Polymorphisms in Genes Coding for Tamoxifen Metabolising Enzymes (CYPTAMBRUT-3)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Vlaamse Vereniging voor Obstetrie en Gynaecologie.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Vlaamse Vereniging voor Obstetrie en Gynaecologie
ClinicalTrials.gov Identifier:
NCT00966043
First received: August 24, 2009
Last updated: NA
Last verified: August 2009
History: No changes posted
  Purpose

CYPTAM-BRUT 3 is a prospective, multicentric study in Belgium within the CYPTAM study of the Leiden University Medical Center (NTR1509) including postmenopausal women receiving tamoxifen for estrogen-receptor positive breast cancer in the adjuvant setting. The primary endpoint is the difference in uterine changes between women with a normal versus low TAS after 3 months of tamoxifen use. Secondary endpoints are serum metabolite concentrations, serum follicle-stimulating hormone level, serum sex hormone-binding globulin level and menopausal symptoms. These patients are registered in the Leiden protocol with time to breast cancer event as primary endpoint.


Condition Intervention Phase
Breast Neoplasms
Female
Biological: blood samples/ ultrasound
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prevalence of Genetic Polymorphisms in Genes Coding for Tamoxifen Metabolising Enzymes, in Postmenopausal ER-positive Breast Cancer Patients According to Uterine and Biochemical Changes and Tolerability of Tamoxifen.

Resource links provided by NLM:


Further study details as provided by Vlaamse Vereniging voor Obstetrie en Gynaecologie:

Primary Outcome Measures:
  • change in endometrial thickness or uterine volume [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tolerability of tamoxifen-HRQoL questionnaire [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]
  • Vaginal bleeding [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]
  • Biochemical changes [ Time Frame: 3-6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: June 2009
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: blood samples/ ultrasound
    blood samples for FSH and SHBG ultrasound of the uterus
Detailed Description:

We will study the impact of the 'tamoxifen activity score' - based on functional genetic polymorphisms for tamoxifen metabolism and the use of drugs that interfere with tamoxifen-against tamoxifen related endpoints like uterine changes and subjective menopausal symptoms.

The prevalence of genetic polymorphisms in the CYP2D6 and other genes and differences in usage of drugs interacting with tamoxifen metabolism will be compared between women with and those without endometrial thickening on one hand and between women with and those without hot flashes on the other hand. Tamoxifen use in adjuvant setting.

  • "Tamoxifen activity score" (23): The endpoints will be correlated with a predefined 'tamoxifen activity score' which is based on the presence of single nucleotide polymorphisms (SNP) in relevant genes combined with the effect of well known drugs that interfere with the metabolism of tamoxifen. The 'tamoxifen activity score' has been associated with tamoxifen compliance by a group in the US (23). The score will be adapted to the Belgian situation based on the prevalence of these SNPs in a Belgian population of volunteers for blood donation and consecutive breast cancer patients.
  • The study setting are postmenopausal women with an early ER- positive breast cancer and not previously treated with an endocrine agent or hormone replacement therapy, with an intact uterus and clearly measurable thin endometrium/uterus. N =250
  Eligibility

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

Inclusion Criteria:

  • Female > 18 years of age
  • Written and voluntary informed consent understood signed and dated
  • Histologically or cytologically confirmed measurable invasive adenocarcinoma of the breast, amenable to curative therapy.
  • Patients must be postmenopausal as defined by criteria in appendix 1.
  • Breast cancer should be considered as oestrogen receptor positive by the clinician using immunohistochemistry readings as is standard procedure for local pathologist
  • Prior endocrine tamoxifen therapy is not allowed
  • Patients are not previously treated with an endocrine agent or hormone replacement therapy needs being stopped for at least 6 months.
  • Prior chemotherapy and radiotherapy is allowed
  • Adequate renal and liver function Serum creatinine and serum bilirubin ≤ 1.5 X ULN Serum ALT and AST ≤ 2.5 X ULN (or ≤ 5 in case of liver metastases)
  • Serum calcium should be ≤ 11,6 mg/dl
  • ECOG performance status 0,1,2 (appendix 2)

Exclusion Criteria:

  • Male
  • Life threatening disease requiring a quick response (eg, extensive hepatic or pulmonary involvement)
  • Use of any endocrine treatment or recent/current use of hormone replacement therapy.
  • Contra indication for tamoxifen: history of DVT/vaginal bleeding of unknown origin
  • Dementia
  • History of other malignancy that may interfere with at least 6 months of tamoxifen therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00966043

Contacts
Contact: Chantal Blomme chantalblomme@hotmail.com
Contact: Ann-Sophie Dieudonne anne-sophie.dieudonne@uz.kuleuven.ac.be

Locations
Belgium
AZ St-Maarten Not yet recruiting
Duffel, Antwerpen, Belgium, 2570
Contact: chantal Blomme       chantalblomme@hotmail.com   
Principal Investigator: Patrick Berteloot         
AZ St-Nikolaas Recruiting
St-Niklaas, Antwerpen, Belgium, 9100
Contact: Goele Wallays       goele.wallays@aznikolaas.be   
Principal Investigator: Willem Lybaert         
Ziekenhuizen Oost-Limburg Camus St-Jan Not yet recruiting
Genk, Limburg, Belgium, 3600
Contact: Patricia Jarkowski       patricia.jarkowski@zol.be   
Principal Investigator: Gregg Vandeputte         
AZ St-Blasius Not yet recruiting
Dendermonde, Ookst-Vlaanderen, Belgium, 9200
Principal Investigator: Jan Decloedt         
Maria-Middelares Not yet recruiting
Gent, Oost-Vlaanderen, Belgium, 9000
Principal Investigator: Johan vanginderachter         
UZ Not yet recruiting
Gent, Oost-Vlaanderen, Belgium, 9000
Contact: Marleen De Block       Marleen.deblock@ugent.be   
Principal Investigator: Rudy Vandenbroecke         
UZ Recruiting
Leuven, Vlaams-Brabant, Belgium, 3000
Contact: Chantal Blomme       chantalblomme@hotmail.com   
Contact: Anne-Sophie Dieudonne       anne-sophie.dieudonne@uz.kuleuven.ac.be   
Heilig-Hart Ziekenhuis Not yet recruiting
Roeselare, West-Vlaanderen, Belgium, 8800
Principal Investigator: Ludo Van der Voort         
Institut Bordet Not yet recruiting
Brussel, Belgium, 1000
Contact: Melanie Demol       melanie.demol@bordet.be   
Principal Investigator: fatima Cardoso         
UZ Not yet recruiting
Brussel, Belgium, 1090
Contact: Alex dewaele       alex.dewaele@uzbrussel.be   
Principal Investigator: Jacques Degreve         
UCL Not yet recruiting
Brussel, Belgium, 1200
Contact: Nathalie Blondeel       nathalie.blondeel@clin.ucl.ac.be   
Principal Investigator: Martine Berlière         
Sponsors and Collaborators
Vlaamse Vereniging voor Obstetrie en Gynaecologie
Investigators
Principal Investigator: Patrick Neven UZ Leuven
  More Information

No publications provided

Responsible Party: Marleens Parisis, VVOG
ClinicalTrials.gov Identifier: NCT00966043     History of Changes
Other Study ID Numbers: Eudract 2009-010059-28., S 51521
Study First Received: August 24, 2009
Last Updated: August 24, 2009
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

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

ClinicalTrials.gov processed this record on April 17, 2014