Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by The Netherlands Cancer Institute
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT00738777
First received: August 19, 2008
Last updated: September 2, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Breast Cancer
Drug: Anastrozole
Drug: Anastrozole+Fulvestrant
Drug: Tamoxifen
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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).

Resource links provided by NLM:


Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • Decrease in tumor cell proliferation and induced apoptosis. [ Time Frame: At baseline and after 2-6 weeks of endocrine treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of changes in gene expression after different endocrine treatment exposures [ Time Frame: At baseline and after endocrine treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: July 2008
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
NKI-AVL Recruiting
Amsterdam, Netherlands, 1066 CX
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   
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 W.M. Laarhoven, MD         
Principal Investigator: Hanneke W.M. Laarhoven, MD         
Sponsors and Collaborators
The Netherlands Cancer Institute
AstraZeneca
Investigators
Principal Investigator: Sabine C Linn, MD NKI-AvL
  More Information

No publications provided

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT00738777     History of Changes
Other Study ID Numbers: N08AFT, EudraCT; 2008-000644-13
Study First Received: August 19, 2008
Last Updated: September 2, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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

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

ClinicalTrials.gov processed this record on October 20, 2014