Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

Sponsor
The Netherlands Cancer Institute (Other)
Overall Status
Suspended
CT.gov ID
NCT00738777
Collaborator
AstraZeneca (Industry)
250
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4
191
62.5
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Study Details

Study Description

Brief Summary

To investigate prospectively whether short term endocrine treatment can induce molecular changes, predictive for therapy response.

Condition or Disease Intervention/Treatment Phase
Phase 2

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

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
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).
Actual Study Start Date :
Jul 1, 2008
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 1

Anastrozole

Drug: Anastrozole
1 mg,QD,PO

Experimental: 2

Anastrozole + Fulvestrant

Drug: Anastrozole+Fulvestrant
Anastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter

Active Comparator: 3

Tamoxifen

Drug: Tamoxifen
loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO

Other: 4

Tamoxifen (pre-menopausal and male patients)

Drug: Tamoxifen
loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO

Outcome Measures

Primary Outcome Measures

  1. Decrease in tumor cell proliferation and induced apoptosis. [At baseline and after 2-6 weeks of endocrine treatment]

Secondary Outcome Measures

  1. Comparison of changes in gene expression after different endocrine treatment exposures [At baseline and after endocrine treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Medisch Centrum Haaglanden den Haag ZH Netherlands
2 NKI-AVL Amsterdam Netherlands 1066 CX
3 St. Antonius ziekenhuis Nieuwegein Netherlands
4 UMC St. Radboud Nijmegen Netherlands

Sponsors and Collaborators

  • The Netherlands Cancer Institute
  • AstraZeneca

Investigators

  • Principal Investigator: Sabine C Linn, MD, NKI-AvL

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT00738777
Other Study ID Numbers:
  • N08AFT
  • EudraCT; 2008-000644-13
First Posted:
Aug 20, 2008
Last Update Posted:
Jan 22, 2021
Last Verified:
Jan 1, 2021
Keywords provided by The Netherlands Cancer Institute
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 22, 2021