Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

• ClinicalTrials.gov Identifier: NCT00738777
• Recruitment Status: Suspended
• First Posted: August 20, 2008
• Last Update Posted: January 22, 2021
• Sponsor: The Netherlands Cancer Institute
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): The Netherlands Cancer Institute

Tracking Information

• First Submitted Date: August 19, 2008
• First Posted Date: August 20, 2008
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: July 2008
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 19, 2008): Decrease in tumor cell proliferation and induced apoptosis. [ Time Frame: At baseline and after 2-6 weeks of endocrine treatment ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: August 19, 2008): Comparison of changes in gene expression after different endocrine treatment exposures [ Time Frame: At baseline and after endocrine treatment ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer
• 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).
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Breast Cancer

Intervention

• Drug: Anastrozole
  1 mg,QD,PO
• Drug: Anastrozole+Fulvestrant
  Anastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter
• Drug: Tamoxifen
  loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO

Study Arms

• Active Comparator: 1
  Anastrozole
  Intervention: Drug: Anastrozole
• Experimental: 2
  Anastrozole + Fulvestrant
  Intervention: Drug: Anastrozole+Fulvestrant
• Active Comparator: 3
  Tamoxifen
  Intervention: Drug: Tamoxifen
• 4
  Tamoxifen (pre-menopausal and male patients)
  Intervention: Drug: Tamoxifen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: August 19, 2008): 250
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT00738777
• Other Study ID Numbers: N08AFT; EudraCT; 2008-000644-13
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: The Netherlands Cancer Institute
• Original Responsible Party: S.C. Linn, MD, NKI-AVL
• Current Study Sponsor: The Netherlands Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: AstraZeneca

Investigators

• Principal Investigator: Sabine C Linn, MD; NKI-AvL

• PRS Account: The Netherlands Cancer Institute
• Verification Date: January 2021