Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer
Primary Purpose
Breast Cancer
Status
Suspended
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Anastrozole
Anastrozole+Fulvestrant
Tamoxifen
Tamoxifen
Sponsored by

About this trial
This is an interventional basic science trial for Breast Cancer focused on measuring pre-operative, endocrine treatment, drug resistance
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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.
Sites / Locations
- Medisch Centrum Haaglanden
- NKI-AVL
- St. Antonius ziekenhuis
- UMC St. Radboud
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Active Comparator
Other
Arm Label
1
2
3
4
Arm Description
Anastrozole
Anastrozole + Fulvestrant
Tamoxifen
Tamoxifen (pre-menopausal and male patients)
Outcomes
Primary Outcome Measures
Decrease in tumor cell proliferation and induced apoptosis.
Secondary Outcome Measures
Comparison of changes in gene expression after different endocrine treatment exposures
Full Information
NCT ID
NCT00738777
First Posted
August 19, 2008
Last Updated
January 20, 2021
Sponsor
The Netherlands Cancer Institute
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT00738777
Brief Title
Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer
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).
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Suspended
Why Stopped
in preparation for an amendment
Study Start Date
July 2008 (Actual)
Primary Completion Date
June 2022 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Netherlands Cancer Institute
Collaborators
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
pre-operative, endocrine treatment, drug resistance
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
250 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Anastrozole
Arm Title
2
Arm Type
Experimental
Arm Description
Anastrozole + Fulvestrant
Arm Title
3
Arm Type
Active Comparator
Arm Description
Tamoxifen
Arm Title
4
Arm Type
Other
Arm Description
Tamoxifen (pre-menopausal and male patients)
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Intervention Description
1 mg,QD,PO
Intervention Type
Drug
Intervention Name(s)
Anastrozole+Fulvestrant
Intervention Description
Anastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Intervention Description
loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Intervention Description
loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO
Primary Outcome Measure Information:
Title
Decrease in tumor cell proliferation and induced apoptosis.
Time Frame
At baseline and after 2-6 weeks of endocrine treatment
Secondary Outcome Measure Information:
Title
Comparison of changes in gene expression after different endocrine treatment exposures
Time Frame
At baseline and after endocrine treatment
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sabine C Linn, MD
Organizational Affiliation
NKI-AvL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medisch Centrum Haaglanden
City
den Haag
State/Province
ZH
Country
Netherlands
Facility Name
NKI-AVL
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
St. Antonius ziekenhuis
City
Nieuwegein
Country
Netherlands
Facility Name
UMC St. Radboud
City
Nijmegen
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer
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