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: March 16, 2015
Last verified: March 2015
  Purpose

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


Condition Intervention Phase
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
Drug: letrozole
Drug: anastrozole
Drug: chemotherapy
Procedure: Surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Pathologic Complete Response (CR) Rate [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    • In patients with Ki67 >10% and <= 15 pg/ml at 4 weeks.
    • The pCR rate 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.

  • Acceptability of Management With Surgical Oophorectomy/Continued LHRH With Continued Oral Endocrine Therapy and no Chemotherapy [ 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.


Secondary Outcome Measures:
  • Relationship Between Pretreatment FFNP-PET Standard Uptake Value (SUV) and 4-week Post-treatment Ki-67 [ Time Frame: Baseline and 4 weeks post-treatment ] [ Designated as safety issue: No ]
  • Preoperative Endocrine Prognostic Index Score (PEPI Score) [ Time Frame: At time of definitive surgery ] [ Designated as safety issue: No ]
    To obtain the PEPI score, risk points for relapse-free survival (RFS) and breast cancer-specific survival (BCSS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).

  • PEPI-0 Rate in Patients Whose Estradiol is Fully Suppressed (< or = 15 pg/mL) and Tumor Ki67 Level is 10% or Less [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: September 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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 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.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01368263

Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Timothy Pluard, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01368263     History of Changes
Other Study ID Numbers: 201106141
Study First Received: June 2, 2011
Results First Received: January 23, 2015
Last Updated: March 16, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Anastrozole
Goserelin
Letrozole
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 27, 2015