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

Stage IIIA Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01368263
• Other study ID #: 201106141
• Status: Terminated
• Phase: Phase 2
• First received: June 2, 2011
• Last updated: March 16, 2015
• Start date: September 2011
• Est. completion date: May 2013

Study information

• Verified date: March 2015
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• 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

Intervention

Drug:
• goserelin acetate
Given SC
• letrozole
Given PO
• anastrozole
Given PO
• chemotherapy
Standard chemotherapy

Procedure:
• Surgery

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response (CR) Rate	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.	1 month	No
Primary	Acceptability of Management With Surgical Oophorectomy/Continued LHRH With Continued Oral Endocrine Therapy and no Chemotherapy	Proportion of patients with a PEPI score of 0 and pathological stage 1 who choose to forego chemotherapy.	6 months post neoadjuvant endocrine therapy and surgery	No
Secondary	Relationship Between Pretreatment FFNP-PET Standard Uptake Value (SUV) and 4-week Post-treatment Ki-67		Baseline and 4 weeks post-treatment	No
Secondary	Preoperative Endocrine Prognostic Index Score (PEPI Score)	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).	At time of definitive surgery	No
Secondary	PEPI-0 Rate in Patients Whose Estradiol is Fully Suppressed (< or = 15 pg/mL) and Tumor Ki67 Level is 10% or Less		16 weeks	No

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine