TRial on the Endocrine Activity of Neoadjuvant Degarelix
Condition: Breast Cancer Invasive Nos
MeSH terms: Breast Neoplasms
Intervention: triptorelin; degarelix; letrozole
Intervention description: Triptorelin 3.75 mg injected into the muscle on day 1 every 28 days for 6 cycles (1 cycle= 28 days); Degarelix 240 mg injected under the skin given as two injections of 120 mg on the first day of treatment, followed by injection of 80 mg on day 1 of cycles 2 to 6 (1 cycle=28 days); Letrozole 2.5 mg orally every day for 6 cycles
Intervention MeSH terms: Letrozole; Triptorelin Pamoate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Premenopausal patients; ER-positive; PgR+ (>50%); HER2-negative or not amplified

Summary:

      The purpose of the this study is to investigate the anti-tumor activity and tolerability of
      the study medications Degarelix and Triptorelin in premenopausal women receiving preoperative
      treatment with Letrozole.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female gender

          -  Premenopausal status measured within 14 days Prior to randomization: Estradiol (E2)
             must be above 54 pg/mL (or above 198 pmol/L

          -  Age ≥ 18 years

          -  Performance Status - Eastern Cooperative Oncology Group (ECOG) 0-1

          -  Histologically confirmed invasive breast cancer: Primary tumor greater than 2 cm
             Diameter, any nodal stage, no evidence of metastasis (M0)

          -  Primary tumor must have ER and PgR >50% of the cells

          -  Primary tumor must be HER2-negative (by IHC and/or ISH)

          -  Hematopoietic status: Absolute neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 100 ×
             109/L, hemoglobin ≥ 9 g/dL

          -  Hepatic status: Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), AST and ALT
             ≤ 2.5 × ULN, Alkaline phosphatase ≤ 2.5 × ULN

          -  Renal status: Creatinine ≤ 1.5 ×ULN

          -  Negative serum pregnancy test, within 2 weeks (preferably 7 days) prior to
             randomization.

          -  The patient must be willing to use effective non-hormonal contraception after the
             pregnancy test and up to surgery. Oral, injectable, or implant hormonal contraceptives
             or medicated IUD are not allowed within 2 months prior to randomization and during the
             trial.

          -  Prior fertility treatment is allowed but must have been stopped at least 12 months
             before randomization.

          -  The patient has completed the baseline patient-reported symptoms questionnaire.

          -  Written Informed Consent (IC) must be signed and dated by the patient and the
             Investigator prior to randomization.

          -  The patient has been informed of and agrees to data transfer and handling, in
             accordance with national data protection guidelines.

          -  The patient accepts blood samples to be taken for the determination of the primary
             endpoint.

          -  The patient agrees to make tumor available for submission for central pathology review
             and for translational studies as part of this protocol

        Exclusion Criteria:

          -  Postmenopausal

          -  Any hormonal treatment (e.g., oral, injectable, implant, or medicated IUD) in the
             previous 2 months

          -  Presence of HER2 overexpression or amplification

          -  Received any prior treatment for primary invasive breast cancer

          -  Received any GnRH analog or SERM or AI within 12 months prior to randomization

          -  A history of malignant neoplasms within the past 10 years, except for curatively
             treated,Basal and squamous cell carcinoma of the skin, carcinoma in situ of the
             cervix, carcinoma in situ of the bladder

          -  Previous ipsilateral breast cancer (invasive or in situ) at any time

          -  Inflammatory breast cancer

          -  Bilateral invasive breast cancer

          -  Known history of uncontrolled or symptomatic angina, clinically significant
             arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled
             hypertension (≥ 180/110), unstable diabetes mellitus, dyspnea at rest, or chronic
             therapy with oxygen

          -  Concurrent disease or condition that would make the subject inappropriate for study
             participation or any serious medical disorder that would interfere with the subject's
             safety

          -  Unresolved or unstable, serious adverse events from prior administration of another
             investigational drug

          -  Active or uncontrolled infection CTCAE v.4 grade 2 or higher

          -  Dementia, altered mental status, or any psychiatric condition that would prevent the
             understanding or rendering of Informed Consent

          -  Treatment with an investigational agent must have stopped at least 30 days before
             randomization.

          -  Pregnant or lactating women; lactation has to stop before randomization.