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Goserelin and Letrozole or Anastrozole in Premenopausal Patients With Stage II-III Estrogen Receptor-Positive Breast Cancer

This study has been terminated.
(Due to funding source and lack of accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01368263
First received: June 2, 2011
Last updated: August 9, 2013
Last verified: August 2013

June 2, 2011
August 9, 2013
September 2011
May 2013   (final data collection date for primary outcome measure)
  • Pathologic CR rates of neoadjuvant chemotherapy in patients with endocrine therapy resistant tumors [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Acceptability of postsurgical treatment regimen which does not include chemotherapy in patients with a PEPI-0 tumor [ Time Frame: 6 months post neoadjuvant endocrine therapy and surgery ] [ Designated as safety issue: No ]
    Proportion of patients with a PEPI score of 0 and pathological stage 1 who choose to forego chemotherapy.
  • Pathologic CR rates of neoadjuvant chemotherapy in patients with endocrine therapy resistant tumors [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Number of patients with a pathologic complete response as a percent of patients who received neoadjuvant chemotherapy.
  • Acceptability of postsurgical treatment regimen which does not include chemotherapy in patients with a PEPI-0 tumor [ Time Frame: 6 months post neoadjuvant endocrine therapy and surgery ] [ Designated as safety issue: No ]
    Proportion of patients with a PEPI score of 0 and pathological stage 1 who choose to forego chemotherapy.
Complete list of historical versions of study NCT01368263 on ClinicalTrials.gov Archive Site
  • Relationship between pretreatment FFNP-PET standard uptake value (SUV) and post-treatment Ki-67 [ Time Frame: Baseline and 4 weeks post-treatment ] [ Designated as safety issue: No ]
  • PEPI score [ Time Frame: At time of definitive surgery ] [ Designated as safety issue: No ]
  • PEPI-0 rate in patients whose estradiol is fully suppressed (< or = 15 pg/mL) and tumor Ki67 level is 10% or less [ Time Frame: 4 weeks and 16 weeks ] [ Designated as safety issue: No ]
    PEPI-0 rate at 4 weeks and 16 weeks Ki67 level 10% or less at 4 weeks
  • Rate of patients who do not respond to endocrine therapy and subsequent treatment management [ Time Frame: At end of 1 month or 16-week endocrine therapy ] [ Designated as safety issue: No ]
  • Relationship between pretreatment FFNP-PET standard uptake value (SUV) and post-treatment Ki-67 [ Time Frame: Baseline and 4 weeks post-treatment ] [ Designated as safety issue: No ]
  • PEPI score [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • PEPI-0 rate in patients whose estradiol is fully suppressed (< 10 pg/mL) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Tumor Ki67 level < 10% [ Time Frame: At 4 weeks ] [ Designated as safety issue: No ]
  • Rate of patients who do not respond to endocrine therapy and subsequent treatment management [ Time Frame: At end of 1 month or 16-week endocrine therapy ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Goserelin and Letrozole or Anastrozole in Premenopausal Patients With Stage II-III Estrogen Receptor-Positive Breast Cancer
A Multisite International Collaborative Phase 2 Study of Neoadjuvant Goserelin and a Non-steroidal Aromatase Inhibitor for Premenopausal Women With Estrogen Receptor Positive HER2 Negative Clinical Stage 2 and 3 Breast Cancer

This phase II trial studies the impact of a presurgical endocrine therapy, consisting of goserelin with letrozole or anastrozole on the treatment of premenopausal patients with stage II-III estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Endocrine therapy reduces the amount of estrogen in the body. E+ breast cancer require estrogen, so lower levels of estrogen may slow or stop cell growth. Giving goserelin together with letrozole or anastrozole before surgery may enhance the effectiveness of, or eliminate the need for, chemotherapy

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Estrogen Receptor-positive Breast Cancer
  • HER2-negative Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Drug: goserelin acetate
    Given SC
    Other Names:
    • ICI-118630
    • ZDX
    • Zoladex
  • Drug: letrozole
    Given PO
    Other Names:
    • CGS 20267
    • Femara
    • LTZ
  • Drug: anastrozole
    Given PO
    Other Names:
    • ANAS
    • Arimidex
    • ICI-D1033
  • Drug: chemotherapy
    Standard chemotherapy
    Other Name: chemo
  • Procedure: Surgery
  • Experimental: Group 1 (Ki67 <10%, E2 <= 15 pg/ml)
    Patients receive 1 cycle (28 days) of endocrine therapy consisting of goserelin acetate SC on day 1 and letrozole or anastrozole PO QD. Neoadjuvant treatment repeats every 28 days for a total of 16-18 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo the appropriate standard surgical procedure to remove the cancer. Recommendations for postsurgical treatment will be based on PEPI score and physician discretion.
    Interventions:
    • Drug: goserelin acetate
    • Drug: letrozole
    • Drug: anastrozole
    • Procedure: Surgery
  • Experimental: Group 2 (Ki67 >= 10%, E2 <= 15 pg/ml)
    Patients receive 1 cycle (28 days) of endocrine therapy consisting of goserelin acetate SC on day 1 and letrozole or anastrozole PO QD. Patients receive standard neoadjuvant chemotherapy in the absence of disease progression or unacceptable toxicity. Patients then undergo the appropriate standard surgical procedure to remove the cancer. Postsurgical treatment at physician discretion.
    Interventions:
    • Drug: goserelin acetate
    • Drug: letrozole
    • Drug: anastrozole
    • Drug: chemotherapy
    • Procedure: Surgery
  • Experimental: Group 3 (E2 > 15 pg/ml)
    Patients receive 1 cycle (28 days) of endocrine therapy consisting of goserelin acetate SC on day 1 and letrozole or anastrozole PO QD. Patients receive standard neoadjuvant therapy at the discretion of the physician. Patients then undergo the appropriate standard surgical procedure to remove the cancer. Postsurgical treatment at physician discretion.
    Interventions:
    • Drug: goserelin acetate
    • Drug: letrozole
    • Drug: anastrozole
    • Drug: chemotherapy
    • Procedure: Surgery
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
8
May 2013
May 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient must have histological or cytological confirmed invasive breast cancer
  • Patient must be premenopausal confirmed by serum estradiol level in the premenopausal range (> 25 pg/ml) at the beginning of the study; for women on oral contraceptives, these agents must be held for two weeks before the estradiol assessment is made
  • Patient must have a negative serum pregnancy test within 7 days of registration
  • Patient's tumor must be ER+ with or without concomitant progesterone receptor-positive (PR+) with an Allred score of 6, 7 or 8; patients with > 66.6% of cells staining positive by conventional immunohistochemistry (IHC) have a minimum Allred score of 6 and are eligible
  • Patient's tumors must be HER2 negative by local laboratory assessment: HER2 IHC 0, 1+, or 2+ with subsequent negative fluorescent in situ hybridization (FISH) (ratio < 1.8); negative FISH alone in absence of IHC is acceptable
  • Patient must have T2-T4c, any N, M0 breast cancer, by clinical staging (physical examination)
  • Patient's primary tumor must be palpable and measure > 2 cm by tape, ruler or caliper measurements in at least one dimension
  • Patient must have mammogram and ultrasound of the breast within 42 days prior to registration; if a patient has clinically palpable or suspicious nodes, then an ultrasound of the axilla is also required
  • Patient, as documented by the treating physician, must be clinically staged as one of the following:

    • T4 a-c for which modified radical mastectomy with negative margins is the goal
    • T2 or T3 for which conversion from needing mastectomy to breast conservation is the goal
    • T2 for which lumpectomy at first attempt is the goal
  • Patient must be > or = 18 years old.
  • Patient must stop taking all forms of hormonal treatment, including oral or other form of hormonal contraceptive methods and all forms of hormone replacement therapy, at least two weeks prior to starting protocol therapy
  • Patient must agree to use a "highly-effective form of non-hormonal contraception" (applies to patient and/or partner)
  • Patient must be willing to undergo oophorectomy, if indicated
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Patient must have normal organ and marrow function as defined below:
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 3.0 X institutional upper limit of normal (ULN)
  • Creatinine within normal institutional limits OR
  • Creatinine clearance >= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • If the patient is a cancer survivor, all of the following criteria must be met
  • Patient has undergone potentially curative therapy from all prior malignancies
  • Patient must have no evidence of any prior malignancies for at least 5 years with no evidence of recurrence (except for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, contralateral ductal carcinoma in situ (DCIS) treated with mastectomy or lumpectomy and radiation but without tamoxifen treatment, or non-melanoma skin cancer with no evidence of recurrence)
  • Patient must be deemed by her treating physician to be at low risk (< 30%) for recurrence from prior malignancies
  • Patient must be able to understand and willing to sign a written informed consent document

Exclusion Criteria:

  • Patient must not have 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)
  • Patient must not have had prior treatment for invasive breast cancer, including radiation, endocrine therapy, chemotherapy, or investigational agent; patients whose diagnosis was established by incision biopsy are not eligible
  • Patient must not have had prior DCIS in the ipsilateral breast
  • Patient must not have used tamoxifen for prior contralateral DCIS
  • Patient must not have any evidence of distant metastasis (M1) on imaging; staging scans are not mandatory but any exams performed as standard of care throughout the study period will be collected for correlation as needed
  • If patient does not agree to undergo mastectomy or lumpectomy after neoadjuvant therapy, she is ineligible for this study
  • Patient must not be receiving other investigational agents or be enrolled in another neoadjuvant clinical trial for treatment of the existing breast cancer
  • Pregnant and/or breastfeeding women are excluded from this study
  • Patient must not have any concurrent life threatening illnesses
  • Patient must not have undergone prior sentinel lymph node surgery; cores or FNA of lymph node are acceptable
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01368263
201106141, NCI-2011-00870
Yes
Washington University School of Medicine
Washington University School of Medicine
National Cancer Institute (NCI)
Principal Investigator: Timothy Pluard Washington University School of Medicine
Washington University School of Medicine
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP