An Observational Study to Assess Response to Tamoxifen (CYPTAMBRUT-2)

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:
NCT00965939
First received: August 24, 2009
Last updated: NA
Last verified: August 2009
History: No changes posted
  Purpose

CYPTAM-BRUT 2 is a prospective, multicentric study including postmenopausal women receiving tamoxifen for metastatic, locally advanced (stage IIIB/C) or in the neoadjuvant setting for measurable estrogen-receptor positive breast cancers. The primary endpoint is the difference in efficacy of tamoxifen, defined as the objective response rate using RECIST criteria, between women with a normal versus low Tamoxifen Activity Score (TAS) after 3-6 months of tamoxifen use. The TAS score is based on the presence of genetic variations and drug interactions. Secondary endpoints are time to progression, clinical benefit, serum metabolite concentrations, endometrial changes and menopausal symptoms. Patients using tamoxifen in the neoadjuvant setting needs being operated between 4-6 months following the start of tamoxifen.


Condition
Breast Neoplasm
Female

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Study to Assess Response to Tamoxifen in (cT3)/ Inoperable Locally Advanced / Metastatic ER-positive BC by the 'Tamoxifen Activity Score' Based on Drug Interaction and Polymorphisms in Genes Coding for Tam. Metabolising Enzymes.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • ORR [ Time Frame: 3 months/ 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • TTP [ Time Frame: 3 months/ 6 months ] [ Designated as safety issue: No ]
  • clinical benefit (CR + PR + SD ≥ 6 months) [ Time Frame: 3 months/6months ] [ Designated as safety issue: No ]
  • Endometrial thickness and uterine volume [ Time Frame: Baseline/ 3 months ] [ Designated as safety issue: No ]
  • Tolerability of tamoxifen-HRQoL questionnaire [ Time Frame: baseline/ 3months ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: February 2009
Detailed Description:

This multi-centre open label single arm non randomized observational study will compare the efficacy in terms of overall response rate and progression free survival of tamoxifen as first line therapy in 3 groups of postmenopausal women with measurable hormone dependent large, locally advanced or metastatic breast cancer. The 3 groups are women with a normal and those with a low 'tamoxifen activity score' based on genetic polymorphisms for CYP2D6 and other genes that are important in the metabolism of tamoxifen using SEQUENOM's MassARRAY technology.

The study is subject to Ethical Commission approval and patient consent. The study will necessitate collection of blood for genetic analyses.

We will investigate the relation between the studied genotype, the use of drugs that interfere with tamoxifen and tamoxifen-related endpoints like regression of metastatic or locally advanced or large oestrogen receptor positive breast cancer in tamoxifen users. The 'tamoxifen activity score' has been used by a group in the US showing a link with tamoxifen compliance. The score will be adapted to the Belgian situation based on the prevalence of polymorphism in a Belgian population. The efficacy of tamoxifen 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 study will be conducted in several clinical sites in Belgium. All patients will receive tamoxifen 20mg daily. Patients with a large operable or inoperable non-metastatic breast cancer will be considered for surgery no more than 4 months on tamoxifen. If operable, they will postoperatively receive the most appropriate adjuvant therapy and for hormone therapy either continue tamoxifen or receive an oral aromatase inhibitor as decided by the clinician. If women with a locally advanced inoperable breast cancer are not operable after the 4 months of neo-adjuvant therapy, another appropriate salvage therapy will be proposed. Women with metastatic breast cancer will continue treatment until clinical or imaging progression or unacceptable toxicity development. Patients that experience progression of their disease as defined by RECIST criteria will receive salvage therapy by an oral aromatase inhibitor if tamoxifen is given in first line but some patients may require another therapy like chemotherapy. The study will require approximately 14 months to recruit and another 7 months to events/data analyses as the estimated time to progression in this setting is 9-12 months if tamoxifen is given as first line endocrine therapy for those in the metastatic setting

  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

Female, with ER-positive breast cancer

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 either large (cT3), locally advanced stage IIIB/C inoperable, or metastatic and not amenable to curative therapy with surgery or radiotherapy.
  • Measurable disease is defined as follows: CT scan for metastatic or locally advanced stage IIIB disease and ultrasound of the breast for operable large size breast cancers where tamoxifen is given for neoadjuvant endocrine 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 in the adjuvant setting is allowed if there is more than 12 months after completion of adjuvant tamoxifen.
  • Prior radiotherapy is allowed but evaluable lesions that have been irradiated need to be progressive before starting in the study
  • Concurrent use of bisphosphonates is allowed if they are started 2 weeks before study start and these drugs should be continued as planned throughout the study
  • 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)
  • CNS involvement
  • Less than 12 months since stopping tamoxifen in the adjuvant setting
  • Previous chemotherapy, tamoxifen or more than one line hormone therapy or targeted therapy for locally advanced/ metastatic breast cancer
  • Bone lesions only
  • One line of prior endocrine therapy with an oral aromatase inhibitor for locally advanced or metastatic breast cancer is not allowed also not if there is clear progression according to RECIST and the clinician judges tamoxifen an appropriate second line 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00965939

Contacts
Contact: Chantal Blomme +32496254974 chantalblomme@hotmail.com
Contact: Ann-Sophie Dieudonné anne-sophie.dieudonne@uz.kuleuven.ac.be

Locations
Belgium
Imelda ziekenhuis Not yet recruiting
Bonheiden, Antwerpen, Belgium, 2820
Contact: ann Pauwels    +3215504868    Sec.oncologie@imelda.be   
Principal Investigator: Wim Wynendaele         
AZ St-Maarten Campus Rooienberg Recruiting
Duffel, Antwerpen, Belgium, 2570
Contact: Chantal Blomme    +32496254974    chantalblomme@hotmail.com   
Principal Investigator: Patrick Berteloot         
Heilig-Hartziekenhuis Not yet recruiting
Lier, Antwerpen, Belgium, 2500
Principal Investigator: Sabine Dobbelaere         
Ziekenhuizen Oost-Limburg campus St-jan Recruiting
Genk, Limburg, Belgium, 3600
Contact: Patricia Jarkowski       patricia.jarkowski@zol.be   
Principal Investigator: Gregg Vandeputte         
Virga Jesse Ziekenhuis Not yet recruiting
Hasselt, Limburg, Belgium, 3500
Principal Investigator: Guye Orye         
AZ St-Blasius Recruiting
Dendermonde, Oost-Vlaanderen, Belgium, 9200
Principal Investigator: Jan Decloedt         
UZ Not yet recruiting
Gent, Oost-Vlaanderen, Belgium, 9000
Contact: Marleen De Block       Marleen.deblock@ugent.be   
Principal Investigator: rudy Vandenbroecke         
Maria-Middelares Recruiting
Gent, Oost-Vlaanderen, Belgium, 9000
Principal Investigator: Johan Vanginderachter         
AZ St-Nikolaas Recruiting
St-Niklaas, Oost-Vlaanderen, Belgium, 9100
Contact: Goele Wallays    03/7602573    Goele.wallays@aznikolaas.be   
Principal Investigator: Willem Lybaert         
UZ Leuven Recruiting
Leuven, Vlaams-Brabant, Belgium, 3000
Contact: Chantal Blomme    +32496254974    chantalblomme@hotmail.com   
Contact: Ann-Sophie Dieudonne       anne-sophie.dieudonne@uz.kuleuven.ac.be   
Principal Investigator: Patrick Neven         
Sub-Investigator: Hans Wildiers         
Heilig-Hartziekenhuis Not yet recruiting
Roeselare, West-Vlaanderen, Belgium, 8800
Principal Investigator: Ludo Van der Voort         
UCL Not yet recruiting
Brussels, 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: Prof. Patrick Neven, UZ Leuven
ClinicalTrials.gov Identifier: NCT00965939     History of Changes
Other Study ID Numbers: S51257, B32220095818
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
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 01, 2014