Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

Phase 2

Suspended

• Conditions: Breast Cancer
• Interventions: Drug: Tamoxifen; Drug: Anastrozole+Fulvestrant; Drug: Anastrozole

• Registration Number: NCT00738777
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

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

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 Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-08-19
• Study First Submitted QC: 2008-08-19
• Study First Posted: 2008-08-20
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-20
• Last Update Posted: 2021-01-22
• Primary Completion: 2022-06
• Study Completion: 2024-06

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 250

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4	Tamoxifen	Tamoxifen (pre-menopausal and male patients)
2	Anastrozole+Fulvestrant	Anastrozole + Fulvestrant
3	Tamoxifen	Tamoxifen
1	Anastrozole	Anastrozole

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Comparison of changes in gene expression after different endocrine treatment exposures	At baseline and after endocrine treatment

Trial Locations

Locations (4)

UMC St. Radboud; 🇳🇱 Nijmegen, Netherlands

NKI-AVL; 🇳🇱 Amsterdam, Netherlands

Medisch Centrum Haaglanden; 🇳🇱 den Haag, ZH, Netherlands

St. Antonius ziekenhuis; 🇳🇱 Nieuwegein, Netherlands