ER-positive Breast CancerCYPTAMBRUT-2NCT00965939
An Observational Study to Assess Response to Tamoxifen in Breast Cancer Patients
An observational study of ER-positive Breast Cancer, run by Vlaamse Vereniging voor Obstetrie en Gynaecologie at 12 sites in Belgium.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- ER-positive Breast Cancer
- How many people
- 300 participants
- Where
- 12 sitesBelgium
- Study dates
- Feb 2009to Dec 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Female, with ER-positive breast cancer
Who may be able to join
- - 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
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- 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)
Who cannot join
- - 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
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- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Belgium12 sites
Imelda ziekenhuis
Bonheiden, Antwerpen, 2820
UCL
Brussels, 1200
AZ St-Blasius
Dendermonde, Oost-Vlaanderen, 9200
AZ St-Maarten Campus Rooienberg
Duffel, Antwerpen, 2570
Ziekenhuizen Oost-Limburg campus St-jan
Genk, Limburg, 3600
Maria-Middelares
Ghent, Oost-Vlaanderen, 9000
UZ
Ghent, Oost-Vlaanderen, 9000
Virga Jesse Ziekenhuis
Hasselt, Limburg, 3500
UZ Leuven
Leuven, Vlaams-Brabant, 3000
Heilig-Hartziekenhuis
Lier, Antwerpen, 2500
Heilig-Hartziekenhuis
Roeselare, West-Vlaanderen, 8800
AZ St-Nikolaas
St-Niklaas, Oost-Vlaanderen, 9100
About this study
Official title: Study to Assess Response to Tamoxifen in (cT3)/ Inoperable Locally Advanced / Metastatic ER-positive Breast Cancer by the 'Tamoxifen Activity Score' Based on Drug Interaction and Polymorphisms in Genes Coding for Tam. Metabolising Enzymes.
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.
Read the 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
- Conditions
- ER-positive Breast Cancer
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
Measured: 3 months/ 6 months
Secondary outcomes (4)
TTP
Measured: 3 months/ 6 months
clinical benefit (CR + PR + SD ≥ 6 months)
Measured: 3 months/6months
Endometrial thickness and uterine volume
Measured: Baseline/ 3 months
Tolerability of tamoxifen-HRQoL questionnaire
Measured: baseline/ 3months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2009 (estimated)
- Study startFeb 2009
- Primary completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ER-positive Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vlaamse Vereniging voor Obstetrie en Gynaecologie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Patrick Neven, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00965939
- Sponsor's protocol ID
- S51257
- Other IDs
- B32220095818
- Acronym
- CYPTAMBRUT-2
- Status last verified
- Oct 2015
- First submitted
- 24 Aug 2009
- Last updated
- 28 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Assess Response to Tamoxifen in (cT3)/ Inoperable Locally Advanced / Metastatic ER-positive Breast Cancer by the 'Tamoxifen Activity Score' Based on Drug Interaction and Polymorphisms in Genes Coding for Tam. Metabolising Enzymes.
- ClinicalTrials.gov ID
- NCT00965939
- Acronym / sponsor ID
- CYPTAMBRUT-2 / S51257
- Conditions
- ER-positive Breast Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Vlaamse Vereniging voor Obstetrie en GynaecologieUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Dec 2014 (actual)
- First posted
- 26 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Female, with ER-positive breast cancer
Key inclusion criteria (12 listed)
- - 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.
Key exclusion criteria (10 listed)
- - 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
ORR
Time frame: 3 months/ 6 months
4 secondary outcomes
TTP
Time frame: 3 months/ 6 months
clinical benefit (CR + PR + SD ≥ 6 months)
Time frame: 3 months/6months
Endometrial thickness and uterine volume
Time frame: Baseline/ 3 months
Tolerability of tamoxifen-HRQoL questionnaire
Time frame: baseline/ 3months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Neven principal investigator
UZ Leuven
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of ER-positive Breast Cancer, run by Vlaamse Vereniging voor Obstetrie en Gynaecologie at 12 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: 3 months/ 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2015; AzTrials last refreshed its copy on 7 Nov 2026.