Pre-Operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer - Full Text View

Sponsors and Collaborators:	The Netherlands Cancer Institute AstraZeneca
Information provided by:	The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:	NCT00738777

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 II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Anastrozole Tamoxifen Tamoxifen citrate Ici 182780

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics 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).

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 2013
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Anastrozole	Drug: Anastrozole 1 mg,QD,PO
2: Experimental Anastrozole + Fulvestrant	Drug: Anastrozole+Fulvestrant Anastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter
3: Active Comparator 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

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

Sponsors and Collaborators

The Netherlands Cancer Institute

AstraZeneca

Investigators

Principal Investigator:

Sabine C Linn, MD

NKI-AVL

More Information

Responsible Party:	NKI-AVL ( S.C. Linn, MD )
Study ID Numbers:	N08AFT, EudraCT; 2008-000644-13
Study First Received:	August 19, 2008
Last Updated:	August 19, 2008
ClinicalTrials.gov Identifier:	NCT00738777
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

Study placed in the following topic categories:

Anastrozole
Skin Diseases
Fulvestrant

Breast Neoplasms
Tamoxifen
Breast Diseases

Additional relevant MeSH terms:

Estrogen Antagonists
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors

Bone Density Conservation Agents
Selective Estrogen Receptor Modulators
Pharmacologic Actions
Estrogen Receptor Modulators
Neoplasms
Neoplasms by Site
Therapeutic Uses
Aromatase Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009