Breast CancerPhase 2NCT00738777
Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer
A Phase 2 study testing Anastrozole, Anastrozole+Fulvestrant and Tamoxifen in people with Breast Cancer, run by The Netherlands Cancer Institute at 4 sites in Netherlands.
Trial summary
To investigate prospectively whether short term endocrine treatment can induce molecular changes, predictive for therapy response. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Anastrozole, Anastrozole+Fulvestrant and Tamoxifen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 4 sitesNetherlands
- Study dates
- Jul 2008to Jun 2024
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with proven invasive adenocarcinoma of the breast
- Any tumor with a size ≥ 1cm (NOT inflammatory breast cancer)
- WHO-performance score 0 or 1
- Written informed consent
Who cannot join
- Clues of metastatic disease by clinical examination according to most recent NABON guidelines
- Multicentric breast cancer
- Inflammatory breast cancer
- Hormone replacement during the last 12 months
- Other systemic treatment during the waiting time till surgery
- Already planned date for surgery within the next 2 weeks
Show all 10Show fewer
- Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol
- Patient's refusal to undergo a core biopsy procedure of the primary tumor before the start of treatment
- NB: a concomitant malignancy within the last five years is not an exclusion criterium, because survival is not the primary endpoint. Just as prior invasive breast cancer or DCIS within the last 15 years is not an exclusion criterium.
- NB: Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during the study.
Trial locations and contacts
4 sites in 1 country.
Netherlands4 sites
NKI-AVL
Amsterdam, 1066 CX
St. Antonius ziekenhuis
Nieuwegein
UMC St. Radboud
Nijmegen
Medisch Centrum Haaglanden
The Hague, South Holland
About this study
Official title: A Randomized, Prospective Trial of 2-6 Weeks Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer: Anastrozole +/- Fulvestrant or Tamoxifen Exposure - Response in Molecular Profile (AFTER-study).
To investigate prospectively whether short term endocrine treatment can induce molecular changes, predictive for therapy response.
Read the detailed description
We will perform a randomized, open-label, single-institution study. It will compare the efficacy of three different endocrine treatment regimens (Anastrozole +/- Fulvestrant or Tamoxifen) in changing proliferation-index and inducing apoptosis during a 2-6 week pre-operative treatment period in breast cancer patients. These results will be correlated to gene expression profiles, phosphorylation status of the ER, SNPs in CYP450 sequences, tamoxifen metabolite concentrations, changes in estrogen serum levels and protein expression patterns.
- Conditions
- Breast Cancer
- Being tested
- Anastrozole, Anastrozole+Fulvestrant, Tamoxifen
- Keywords
- pre-operative, endocrine treatment, drug resistance
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnastrozoleDrug
1 mg,QD,PO
Anastrozole+FulvestrantDrug
Anastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter
TamoxifenDrug
loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO
TamoxifenDrug
loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Anastrozole Receives: Drug: Anastrozole |
| 2 | Experimental | Anastrozole + Fulvestrant Receives: Drug: Anastrozole+Fulvestrant |
| 3 | Active comparator | Tamoxifen Receives: Drug: Tamoxifen |
| 4 | Other | Tamoxifen (pre-menopausal and male patients) Receives: Drug: Tamoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in tumor cell proliferation and induced apoptosis.
Measured: At baseline and after 2-6 weeks of endocrine treatment
Secondary outcomes (1)
Comparison of changes in gene expression after different endocrine treatment exposures
Measured: At baseline and after endocrine treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2008 (estimated)
- Study startJul 2008
- Primary completionJun 2022 (estimated)
- Study completionJun 2024 (estimated)
Why it stopped: in preparation for an amendment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Sabine C Linn, MD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00738777
- Sponsor's protocol ID
- N08AFT
- Other IDs
- EudraCT; 2008-000644-13
- Status last verified
- Jan 2021
- First submitted
- 19 Aug 2008
- Last updated
- 22 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Reinema FV, Sweep FCGJ, Adema GJ, Peeters WJM, Martens JWM, Bussink J, Span PN. Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer. Cancer Metab. 2023 Feb 8;11(1):3. doi: 10.1186/s40170-023-00304-4.
PubMed 36755288
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Prospective Trial of 2-6 Weeks Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer: Anastrozole +/- Fulvestrant or Tamoxifen Exposure - Response in Molecular Profile (AFTER-study).
- ClinicalTrials.gov ID
- NCT00738777
- Acronym / sponsor ID
- N08AFT
- Conditions
- Breast Cancer
- Keywords
- pre-operative, endocrine treatment, drug resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: in preparation for an amendment
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Jul 2008 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 20 Aug 2008 (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.
To investigate prospectively whether short term endocrine treatment can induce molecular changes, predictive for therapy response.
Detailed description
We will perform a randomized, open-label, single-institution study. It will compare the efficacy of three different endocrine treatment regimens (Anastrozole +/- Fulvestrant or Tamoxifen) in changing proliferation-index and inducing apoptosis during a 2-6 week pre-operative treatment period in breast cancer patients. These results will be correlated to gene expression profiles, phosphorylation status of the ER, SNPs in CYP450 sequences, tamoxifen metabolite concentrations, changes in estrogen serum levels and protein expression patterns.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: AnastrozoleAnastrozole |
| 2 | Experimental | Drug: Anastrozole+FulvestrantAnastrozole + Fulvestrant |
| 3 | Active comparator | Drug: TamoxifenTamoxifen |
| 4 | Other | Drug: TamoxifenTamoxifen (pre-menopausal and male patients) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with proven invasive adenocarcinoma of the breast
- Any tumor with a size ≥ 1cm (NOT inflammatory breast cancer)
- WHO-performance score 0 or 1
- Written informed consent
Key exclusion criteria (10 listed)
- Clues of metastatic disease by clinical examination according to most recent NABON guidelines
- Multicentric breast cancer
- Inflammatory breast cancer
- Hormone replacement during the last 12 months
- Other systemic treatment during the waiting time till surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anastrozole1 mg,QD,PO | Drug | 1 |
| Anastrozole+FulvestrantAnastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter | Drug | 2 |
| Tamoxifenloading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO | Drug | 3 |
| Tamoxifenloading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO | Drug | 4 |
Primary outcome
Decrease in tumor cell proliferation and induced apoptosis.
Time frame: At baseline and after 2-6 weeks of endocrine treatment
1 secondary outcome
Comparison of changes in gene expression after different endocrine treatment exposures
Time frame: At baseline and after endocrine treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
- Derived from this study: PubMed 36755288Reinema FV, Sweep FCGJ, Adema GJ, Peeters WJM, Martens JWM, Bussink J, Span PN. Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer. Cancer Metab. 2023 Feb 8;11(1):3. doi: 10.1186/s40170-023-00304-4.
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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.
Sabine C Linn, MD principal investigator
The Netherlands Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anastrozole, Anastrozole+Fulvestrant and Tamoxifen in people with Breast Cancer, run by The Netherlands Cancer Institute at 4 sites in Netherlands.
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 4 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: paused, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Decrease in tumor cell proliferation and induced apoptosis. (time frame: At baseline and after 2-6 weeks of endocrine treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00738777, which also lists 1 linked publication.
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 22 Jan 2021.