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Exemestane, Letrozole, or Anastrozole in Treating Postmenopausal Women Who Are Undergoing Surgery for Stage II or Stage III Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00265759
First received: December 14, 2005
Last updated: February 14, 2017
Last verified: February 2017
  Purpose

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane, letrozole, or anastrozole, may fight breast cancer by lowering the amount of estrogen the body makes. Giving exemestane, letrozole, or anastrozole before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether exemestane, letrozole, or anastrozole is more effective in treating breast cancer.

PURPOSE: This randomized phase III trial is studying exemestane, letrozole, and anastrozole to compare how well they work in treating postmenopausal women who are undergoing surgery for stage II or stage III breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: anastrozole
Drug: exemestane
Drug: letrozole
Procedure: Therapeutic Conventional Surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial Comparing 16 to 18 Weeks of Neoadjuvant Exemestane (25 mg Daily), Letrozole (2.5 mg), or Anastrozole (1 mg) in Postmenopausal Women With Clinical Stage II and III Estrogen Receptor Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Clinical Response (Complete or Partial Response) Rate (Cohort A) [ Time Frame: Up to 18 weeks ]
    The clinical response rate (percentage) of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose disease meets the WHO criteria for complete or partial response prior to surgery divided by the total number of eligible patients randomized to that treatment. For each treatment arm, a 95% binomial confidence interval will be constructed for the true clinical response rate. Complete Response (CR): The disappearance of all known disease based on a comparison between the measurements at baseline and the Week 16 visit. Partial Response (PR): A 50% or greater decrease in the product of the bi-dimensional measurements of the lesion (total tumor size) based on a comparison between the measurements at baseline and the Week 16 visit. In addition there can be no appearance of new lesions or progression of any lesion.

  • Anti-tumor Effect in Terms of Pathologic CR (pCR) Rate to Neoadjuvant Chemotherapy (Cohort B) [ Time Frame: Up to 18 weeks ]
    The primary aim is to assess the anti-tumor effect in terms of pathologic CR rates of neo-adjuvant chemotherapy in patients with T2-T4c, any N, M0 breast cancer (by clinical staging) who are endocrine therapy resistant (that is, their Ki-67 level is >10 after 2-4 week of neo-adjuvant endocrine therapy alone). The pCR rate (percentage) for neo-adjuvant chemotherapy is defined as 100 times the number of eligible patients with no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary or sentinel lymph nodes divided by the total number of eligible patients who received neo-adjuvant chemotherapy.


Secondary Outcome Measures:
  • Toxicity (Cohort A) [ Time Frame: Up to 30 days after drug therapy ]
    Incidence of the most common grade 3+ toxicities reported to be probably, possibly, or definitely related to treatment as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (Cohort A) At each treatment evaluation, the type, severity, and attribution of each adverse event reported will be assessed using the NCI-CTCAE definitions. For each treatment, the percentage of patients who developed a severe (grade 3+) toxicity considered possibly, probably or definitively related to treatment will be determined.

  • Progression-free Survival (PFS) (Cohort A and B) [ Time Frame: assessed up to 10 years ]
  • Rate of Improved Surgical Outcome for Patients Considered Marginal for Breast Conservation Surgery Prior to Therapy (Cohort A) [ Time Frame: At time of surgery up to 18 weeks ]
    The rate (percentage) of improved surgical outcome for patients considered marginal for breast conservation surgery prior to therapy for Cohort A is reported below for each treatment arm. Breast conservation surgery (not mastectomy) as the most extensive surgery performed for a patient is considered an improvement in surgical outcome.

  • Rate of Downstaging to Stage I Determined by Sentinel Node Evaluation (Cohort A) [ Time Frame: At time of surgery up to 18 weeks ]
    The rate downstaging to Stage I of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose surgically findings are such that the maximum dimension of the invasive lesion contained in their surgical specimen is at most 2 cm and their lymph nodes are negative (by Hematoxylin & Eosin Staining) divided by the total number of eligible patients randomized to that treatment. For each neo-adjuvant endocrine treatment pair, a 95% binomial confidence interval will be constructed for the true difference in the rate of downstaging to Stage I between these 2 treatments.

  • Rate of Lymph Node Involvement (LNI) (Cohort A) [ Time Frame: At time of surgery up to 18 weeks ]
    For those patients who undergo a sentinel lymph node dissection or an axillary lymph node dissection (at least 6 nodes examined with Hematoxylin & Eosin Staining), the LNI rate (percentage) is defined as 100 times the proportion of eligible patients randomized to that treatment with at least one positive node. For each neo-adjuvant endocrine treatment, a 95% binomial confidence interval will be constructed for its true LNI rate.

  • The Pathologic Complete Response (pCR) Rate (Cohort A) [ Time Frame: At time of surgery up to 18 weeks ]
    The pathologic complete response is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or sentinel lymph nodes. The pathologic complete response rate (percentage) of a given treatment is defined as 100 times the number of eligible patients randomized to that treatment whose surgical specimen is such that there is no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or sentinel lymph nodes divided by the total number of eligible patients randomized to that treatment. For each neo-adjuvant endocrine treatment pair, a 95% binomial confidence interval will be constructed for the true difference in the pCR between these 2 treatments.

  • Clinical Response Rate (Cohort B) [ Time Frame: Up to 18 weeks ]
    The clinical response rate is defined as 100 times the number of eligible patients whose disease meets the WHO criteria for complete or partial response prior to surgery divided by the total number of eligible patients. A 90% binomial confidence interval will be constructed for the true clinical response rate.

  • Rate of Improved Surgical Outcome for Patients Designated as Candidates for Mastectomy Prior to Therapy (Cohort A) [ Time Frame: At time of surgery up to 18 weeks ]
    Rate (percentage) of Improved surgical outcome for patients designated as candidates for mastectomy prior to therapy (Cohort A). Breast conservation surgery (not mastectomy) as the most extensive surgery performed for a patient is considered an improvement in surgical outcome.

  • Overall Survival (Cohort A and B) [ Time Frame: assessed up to 10 years ]
    Overall survival (OS) will be measured from the date of randomization until the date of death. The distribution of overall survival times will be estimated using the Kaplan-Meier method.


Enrollment: 622
Study Start Date: January 2006
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral exemestane once daily for up to 16-18 weeks.
Drug: exemestane
Given PO
Procedure: Therapeutic Conventional Surgery
Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection
Experimental: Arm II
Patients receive oral letrozole once daily for up to 16-18 weeks.
Drug: letrozole
Given PO
Procedure: Therapeutic Conventional Surgery
Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection
Experimental: Arm III
Patients receive oral anastrozole once daily for up to 16-18 weeks.
Drug: anastrozole
Given PO
Procedure: Therapeutic Conventional Surgery
Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of breast cancer

    • T2-T4c, any N, M0 disease
  • Clinically staged, as documented by the treating physician, as 1 of the following:

    • T4a-c disease for which modified radical mastectomy with negative margins is the goal
    • T2 or T3 disease for which conversion from needing mastectomy to breast conservation is the goal
    • T2 disease for which lumpectomy at first attempt is the goal
  • Primary tumor must be palpable and measure > 2 cm by tape, ruler, or caliper measurements in at least one dimension
  • Must agree to undergo mastectomy or lumpectomy after neoadjuvant aromatase inhibitor therapy
  • No inflammatory breast cancer, defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema)
  • No distant metastasis (M1)

    • Isolated ipsilateral supraclavicular node involvement allowed
  • No diagnosis that was established by incisional biopsy
  • Must have estrogen receptor (ER) positive tumor with an Allred score of 6, 7 or 8

    • Patients with > 66.66% (two-thirds) of cells staining positive and have a minimum Allred score of 6 are eligible

PATIENT CHARACTERISTICS:

  • ECOG/Zubrod performance status of ≤ 2
  • Female
  • Patient must be postmenopausal, verified by 1 of the following:

    • Bilateral surgical oophorectomy
    • No spontaneous menses ≥ 1 year
    • No menses for < 1 year with FSH and estradiol levels in postmenopausal range
  • No other malignancies within the past 5 years, except for successfully treated cervical carcinoma in situ; lobular carcinoma in situ of the breast; contralateral ductal carcinoma in situ that was treated with mastectomy or lumpectomy with radiotherapy (without tamoxifen); or non-melanoma skin cancer with no evidence of recurrence

    • Must have undergone potentially curative therapy for all prior malignancies AND deemed to be at low risk for recurrence, according to the treating physician

PRIOR CONCURRENT THERAPY:

  • No prior treatment for invasive breast cancer, including radiotherapy, endocrine therapy, chemotherapy, or investigational agents
  • No prior sentinel lymph node biopsy (cohort B only)
  • At least 1 week since prior agents with estrogenic or putatively estrogenic properties, including herbal preparations
  • At least 1 week since prior hormone replacement therapy of any type, megestrol acetate, or raloxifene
  • No concurrent enrollment in another neoadjuvant clinical trial for treatment of the existing breast cancer
  • No other concurrent anti-neoplastic therapy, including chemotherapy or radiotherapy
  • No concurrent agents or herbal products that alter ER function
  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: NCT00265759

Locations
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Doctor's Hospital of Laredo
Laredo, Texas, United States, 78041
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Investigators
Study Chair: Matthew J. Ellis, MD, PhD, FRCP Washington University Siteman Cancer Center
  More Information

Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00265759     History of Changes
Obsolete Identifiers: NCT00698971
Other Study ID Numbers: ACOSOG-Z1031
CDR0000456382 ( Registry Identifier: NCI Physician Data Query )
Study First Received: December 14, 2005
Results First Received: February 14, 2017
Last Updated: February 14, 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
estrogen receptor-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Exemestane
Anastrozole
Estrogens
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Hormones

ClinicalTrials.gov processed this record on April 21, 2017