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

NCT01368263 | Terminated Phase 2 Results DMC

• 1 other identifier: 201106141
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (3)

• Relationship Between Pretreatment FFNP-PET Standard Uptake Value (SUV) and 4-week Post-treatment Ki-67

  Baseline and 4 weeks post-treatment

• Preoperative Endocrine Prognostic Index Score (PEPI Score)

  At time of definitive surgery

• PEPI-0 Rate in Patients Whose Estradiol is Fully Suppressed (< or = 15 pg/mL) and Tumor Ki67 Level is 10% or Less

  16 weeks

Study Arms (3)

Group 1 (Ki67 <10%, E2 <= 15 pg/ml)

EXPERIMENTAL

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; Drug: letrozole; Drug: anastrozole; Procedure: Surgery

Group 2 (Ki67 >= 10%, E2 <= 15 pg/ml)

EXPERIMENTAL

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; Drug: letrozole; Drug: anastrozole; Drug: chemotherapy; Procedure: Surgery

Group 3 (E2 > 15 pg/ml)

EXPERIMENTAL

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; Drug: letrozole; Drug: anastrozole; Drug: chemotherapy; Procedure: Surgery

Interventions

goserelin acetate DRUG

Given SC

Also known as: ICI-118630, ZDX, Zoladex

Group 1 (Ki67 <10%, E2 <= 15 pg/ml); Group 2 (Ki67 >= 10%, E2 <= 15 pg/ml); Group 3 (E2 > 15 pg/ml)

letrozole DRUG

Given PO

Also known as: CGS 20267, Femara, LTZ

Group 1 (Ki67 <10%, E2 <= 15 pg/ml); Group 2 (Ki67 >= 10%, E2 <= 15 pg/ml); Group 3 (E2 > 15 pg/ml)

anastrozole DRUG

Given PO

Also known as: ANAS, Arimidex, ICI-D1033

Group 1 (Ki67 <10%, E2 <= 15 pg/ml); Group 2 (Ki67 >= 10%, E2 <= 15 pg/ml); Group 3 (E2 > 15 pg/ml)

chemotherapy DRUG

Standard chemotherapy

Also known as: chemo

Group 2 (Ki67 >= 10%, E2 <= 15 pg/ml); Group 3 (E2 > 15 pg/ml)

Surgery PROCEDURE

Group 1 (Ki67 <10%, E2 <= 15 pg/ml); Group 2 (Ki67 >= 10%, E2 <= 15 pg/ml); Group 3 (E2 > 15 pg/ml)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Goserelin; Letrozole; Anastrozole; Drug Therapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Timothy Pluard, M.D.
• Organization: Washington University School of Medicine

tpluard@saint-lukes.org

314-362-5645

Study Officials

• Timothy Pluard, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2011
• First Posted: June 7, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: April 3, 2015
• Results First Posted: February 20, 2015

Record last verified: 2015-03

Locations

US (1)