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Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

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ClinicalTrials.gov Identifier: NCT00738777
Recruitment Status : Recruiting
First Posted : August 20, 2008
Last Update Posted : September 14, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

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
Breast Cancer Drug: Anastrozole Drug: Anastrozole+Fulvestrant Drug: Tamoxifen 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  (Clinical Trial)
Estimated 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 : July 2008
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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
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. [ Time Frame: 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 [ Time Frame: At baseline and after endocrine treatment ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00738777


Contacts
Contact: Sabine C Linn, MD +31-20-5129111 ext 2591 s.linn@nki.nl
Contact: Rutger HT Koornstra, MD +31-20-5129111 ext 6900 r.koornstra@nki.nl

Locations
Netherlands
Medisch Centrum Haaglanden Recruiting
den Haag, ZH, Netherlands
Contact: H M Oosterkamp, MD         
Principal Investigator: H M Oosterkamp, MD         
NKI-AVL Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Sabine C Linn, MD    +31-20-5129111 ext 2591    s.linn@nki.nl   
Contact: Annelot van Rossum, MD    +31-20-5129111 ext 2004    a.v.rossum@nki.nl   
Principal Investigator: Sabine C Linn, MD         
St. Antonius ziekenhuis Not yet recruiting
Nieuwegein, Netherlands
Contact: Paul C de Jong, MD         
Principal Investigator: Paul C de Jong, MD         
UMC St. Radboud Recruiting
Nijmegen, Netherlands
Contact: Hanneke WM Laarhoven, MD         
Principal Investigator: Hanneke WM Laarhoven, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
AstraZeneca
Investigators
Principal Investigator: Sabine C Linn, MD NKI-AvL
More Information

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT00738777     History of Changes
Other Study ID Numbers: N08AFT
EudraCT; 2008-000644-13
First Posted: August 20, 2008    Key Record Dates
Last Update Posted: September 14, 2017
Last Verified: September 2017

Keywords provided by The Netherlands Cancer Institute:
pre-operative
endocrine treatment
drug resistance

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Estradiol
Tamoxifen
Fulvestrant
Anastrozole
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists
Estrogens
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action