Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

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).

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

Study Overview

• Status: Suspended
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anastrozole; Drug: Anastrozole+Fulvestrant; Drug: Tamoxifen

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 Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • NKI-AVL
  • Nieuwegein, Netherlands
    • St. Antonius Ziekenhuis
  • Nijmegen, Netherlands
    • UMC St. Radboud
  • ZH
    • den Haag, ZH, Netherlands
      • Medisch Centrum Haaglanden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decrease in tumor cell proliferation and induced apoptosis.	At baseline and after 2-6 weeks of endocrine treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of changes in gene expression after different endocrine treatment exposures	At baseline and after endocrine treatment

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Sabine C Linn, MD, NKI-AVL

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2008
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: August 19, 2008
• First Submitted That Met QC Criteria: August 19, 2008
• First Posted (Estimate): August 20, 2008

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: drug resistance; pre-operative; endocrine treatment
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Fulvestrant; Tamoxifen; Anastrozole
• Other Study ID Numbers: N08AFT; EudraCT; 2008-000644-13