Arimidex/Tamoxifen Neo Adjuvant Study in Premenopausal Patients With Breast Cancer Under Anti Hormonal Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00605267
First received: January 9, 2008
Last updated: August 3, 2012
Last verified: August 2012
  Purpose

The purpose of this multi-centre, randomised, double-blind, parallel-group study is to compare efficacy and safety between anastrozole and tamoxifen in pre- and post-operative administration under goserelin acetate treatment for premenopausal breast cancer patients


Condition Intervention Phase
Breast Cancer
Drug: Tamoxifen
Drug: Anastrazole (Arimidex)
Drug: Goserelin acetate (Zoladex)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Multi-centre, Randomised, Double-blind, Parallel-group Study to Compare Efficacy and Safety Between Anastrozole (ZD1033) and Tamoxifen in Pre- and Post-operative Administration Under Goserelin Acetate Treatment for Premenopausal Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Best Overall Response Rate (BORR) (Calliper) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from calliper measurement).

    CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by Calliper: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.


  • Best Overall Response Rate (BORR) (US) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from ultra sound (US) measurement).

    CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by US: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.


  • Best Overall Response Rate (BORR) (MRI/CT) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

    The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period(based on the data from magnetic resonance imaging (MRI) or computed tomography (CT) measurement).

    CR (or PR) criteria are met at either 12 weeks or 24 weeks. Per RECIST Criteria (V1.0) and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.



Secondary Outcome Measures:
  • Bone Mineral Density (BMD) Lumbar Spine [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: Yes ]
    Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at lumbar spine.

  • Bone Mineral Density (BMD) Cervical Thighbone [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: Yes ]
    Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at cervical thighbone.

  • Bone Turnover Marker (BAP) EIA Method [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: Yes ]
    Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by EIA method

  • Bone Turnover Marker (BAP) CLEIA Method [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: Yes ]
    Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by CLEIA method

  • Bone Turnover Marker (NTX) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: Yes ]
    Change from baseline in serum crosslinked N-Telopeptide of type I collagen (NTX) at 24 weeks

  • Serum Oestrone (E1) Concentrations [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]
    Ratio of serum Oestrone (E1) concentration (pg/mL) in the ITT population from baseline at 24 weeks.

  • Serum Oestradiol (E2) Concentrations [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]
    Ratio of serum Oestradiol (E2) concentration (pg/mL) in the ITT population from baseline at 24 weeks.

  • Oestrogen Receptor (ER) Status [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]
    ER status in the ITT population is categorized as Positive or Negative

  • Progesterone Receptor (PgR) Status [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]
    PgR status in the ITT population is categorized as Positive or Negative.

  • Human Epidermal Growth Factor Receptor 2 (HER2) Status [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]
    HER2 status in the ITT population is categorized as Positive or Negative

  • Histopathological Response Rate (HRR) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]
    Number of patients in the ITT population defined as histopathological responders over the total number of patients x 100. An histopathological responder = a patient classified as Grade 1b, 2 or 3 for the histopathological response (Grade 0 = no response, 1a = mild response, 1b = moderate response, 2 = marked response or 3 = complete response)

  • Functional Assessment of Cancer Therapy-Breast (FACT-B) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]

    Change from baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B)in the ITT population at 24 weeks. Trial Outcome Index (TOI) = the sum of the Physical Well-Being (PWB), Functional Well-Being (FWB), and Breast Cancer Scale (BCS) subscales of FACT-B.

    FACT-B includes 36 questions; 7 in PWB (Physical Well-Being); 7 inSWB (Social / Family Well-Being); 6 in EWB (Emotional Well-Being); 7 in FWB (Functional Well-Being); 9 in BCS (Breast Cancer Subscale).

    Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier.

    Score range; 0-28 in PWB; 0-28 in SWB; 0-24 in EWB; 0-28 in FWB; 0-36 in BCS; 0-92 in TOI.


  • Endocrine Subscale (ES) [ Time Frame: Assessed at baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]

    Change from baseline in Endocrine Symptom Subscale (ES)) in the ITT population at 24 weeks. ES score = the sum of the responses to all the questions on ES, low scores reflect poor quality of life and high scores reflects better quality of life.

    Score range: 0-72


  • Anastrozole Plasma Concentrations (Cmin) [ Time Frame: Assessed at week 12 ] [ Designated as safety issue: No ]
    Trough Plasma concentrations (Cmin) of Anastrozole - only Anastrozole arm was evaluated for Trough Plasma concentrations.


Enrollment: 197
Study Start Date: October 2007
Study Completion Date: December 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Tamoxifen
Drug: Tamoxifen
20 mg once daily oral dose
Other Name: NOLVADEX
Drug: Goserelin acetate (Zoladex)
3.6mg/month depot injection
Other Name: ZOLADEX
Experimental: 2
Anastrazole (Arimidex)
Drug: Anastrazole (Arimidex)
1 mg once daily oral dose
Other Names:
  • ARIMIDEX
  • ZD1033
Drug: Goserelin acetate (Zoladex)
3.6mg/month depot injection
Other Name: ZOLADEX

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Premenopausal, estrogen receptor positive women, aged 20 years and over, with operable and measurable breast cancer who have provided written informed consent

Exclusion Criteria:

  • Medical history of chemotherapy or endocrine therapy for breast cancer, or with treatment history of radiotherapy. Unwillingness to stop taking any drug known to affect sex hormone status (including hormone replacement therapy (HRT).
  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: NCT00605267

Locations
Japan
Research Site
Hakata, Fukuoka, Japan
Research Site
Kumamoto, Japan
Research Site
Nagoya, Japan
Research Site
Osaka, Japan
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Toshiyuki Kihara Clinical
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00605267     History of Changes
Other Study ID Numbers: D539BC00001
Study First Received: January 9, 2008
Results First Received: November 26, 2010
Last Updated: August 3, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by AstraZeneca:
Breast Cancer
Breast Neoplasms
Tumors or cancer of the human BREAST
Tumor or cancer of the human MAMMARY GLAND

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

ClinicalTrials.gov processed this record on July 24, 2014