Trial record 1 of 1 for:
z1031
Exemestane, Letrozole, or Anastrozole in Treating Postmenopausal Women Who Are Undergoing Surgery for Stage II or Stage III Breast Cancer
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00265759 |
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Recruitment Status :
Completed
First Posted : December 15, 2005
Results First Posted : March 30, 2017
Last Update Posted : February 12, 2020
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Sponsor:
Alliance for Clinical Trials in Oncology
Collaborators:
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
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Brief Summary:
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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer | Drug: anastrozole Drug: exemestane Drug: letrozole Procedure: Therapeutic Conventional Surgery | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 622 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| 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 |
| Actual Study Start Date : | January 2006 |
| Actual Primary Completion Date : | August 2012 |
| Actual Study Completion Date : | November 27, 2019 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I
Patients receive oral exemestane once daily for up to 16-18 weeks.
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Drug: exemestane
Given PO Procedure: Therapeutic Conventional Surgery Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection |
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Experimental: Arm II
Patients receive oral letrozole once daily for up to 16-18 weeks.
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Drug: letrozole
Given PO Procedure: Therapeutic Conventional Surgery Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection |
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Experimental: Arm III
Patients receive oral anastrozole once daily for up to 16-18 weeks.
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Drug: anastrozole
Given PO Procedure: Therapeutic Conventional Surgery Undergo partial or radical mastectomy or lumpectomy with or without lymph node dissection |
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.
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
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Diagnosis of breast cancer
- T2-T4c, any N, M0 disease
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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)
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No distant metastasis (M1)
- Isolated ipsilateral supraclavicular node involvement allowed
- No diagnosis that was established by incisional biopsy
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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
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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
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 |
Publications of Results:
| Responsible Party: | Alliance for Clinical Trials in Oncology |
| ClinicalTrials.gov Identifier: | NCT00265759 |
| Obsolete Identifiers: | NCT00698971 |
| Other Study ID Numbers: |
ACOSOG-Z1031 ACOSOG-Z1031 CDR0000456382 ( Registry Identifier: NCI Physician Data Query ) |
| First Posted: | December 15, 2005 Key Record Dates |
| Results First Posted: | March 30, 2017 |
| Last Update Posted: | February 12, 2020 |
| Last Verified: | February 2020 |
Keywords provided by Alliance for Clinical Trials in Oncology:
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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:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Letrozole Anastrozole Exemestane 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 Hormones Antineoplastic Agents, Hormonal |