Premenopausal patients with histologically confirmed locally advanced breast cancer and with primary tumor of ER+/PgR+ and HER2 negative or not amplified.
Conditions
Interventions
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: TRIPTORELIN ACETATE
CAS Number: 140194-24-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration nu
Sponsors
International Breast Cancer Study Group (IBCSG)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Female gender •Premenopausal status determined locally: -Estradiol (E2) above 54 pg/mL (or above 198 pmol/l),measured =14 days prior to randomization -If estradiol (E2) is =54 pg/mL, but the patient cannot be regarded as postmenopausal, estradiol testing should be repeated to confirm eligibility •Age = 18 years •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or1. •Histologically confirmed invasive breast cancer: -Primary tumor greater than 2 cm diameter, measured by clinical examination and mammography or echography (cT2-4b) -Any N -No evidence of metastasis (M0) •Primary tumor must have ER and PgR >50% of the cells •Primary tumor must be HER2 negative or not amplified •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). In the case of known Gilbert’s syndrome, a higher serum total bilirubin (=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Postmenopausal patients. •Any hormonal treatment (either oral, injectable, implant, or medicated IUD) in the previous 2 months. •Presence of HER2/neu 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 • Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated: -Basal and squamous cell carcinoma of the skin -Carcinoma in situ of the cervix -Carcinoma in situ of the bladder •Diagnosis of 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the endocrine activity of neoadjuvant letrozole plus either degarelix or triptorelin.;Secondary Objective: To evaluate: - Tolerability: - Changes of Ki-67 proliferation marker - The Preoperative Endocrine Prognostic Index (PEPI) score - Best overall (disease) response: defined as best response recorded from the start of treatment across all time points until disease progression. - Node negative disease at surgery. - Breast-conserving surgery (BCS) rate. - Patient reported symptoms (PRS) outcomes. ;Primary end point(s): Time to optimal ovarian function suppression: time from first injection of degarelix or triptorelin to the first assessment of estradiol (E2) level in the range of optimal ovarian function suppression (<10 pg/mL) during the 6 cycles of neoadjuvant treatment. Data for patients who do not reach the targeted E2 level will be censored at the last E2 evaluation date.;Timepoint(s) of evaluation of this end point: E2 levels will be determined at day 1 of the first treatment cycle before the administration of the first dose of degarelix or triptorelin (baseline), and thereafter at 24 and 72 hours, 7 days and 14 days after the first injection, and on day 1 of cycles 2 to 6 before the administration of degarelix or triptorelin. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate: - Tolerability: adverse events according to CTCAE version 4 - Changes of Ki-67 proliferation marker - The Preoperative Endocrine Prognostic Index (PEPI) score - Best overall (disease) response: defined as best response recorded from the start of treatment across all time points until disease progression. - Node negative disease at surgery - Breast-conserving surgery (BCS) rate. - Patient reported symptoms (PRS) outcomes.;Timepoint(s) of evaluation of this end point: Tolerability:The frequencies of AEs by type & worst grade experienced while on the neoadjuvant treatments will be summarized & tabulated by treatment arms -Percentage change in Ki67 expression from pre-treatment to surgery (24 weeks) summarized for each treatment arm -PEPI scores assessed at the time of surgery (24weeks) for both treatment arms -Best overall response including complete response,partial response,stable disease&progressive disease is gathered at the end of 3rd (12weeks) & 6th (24weeks)cycle of each treatment arm -Node negative disease at surgery(after 24weeks) descriptively summarized by treatment arm -BCS at surgery after 24weeks -PRS scores measured at baseline, day1 of cycle2 (8weeks) and cycle4 (16weeks) of triptorelin or degarelix administration & prior surgery | — |
Countries
Italy
Contacts
Public ContactIBCSG Coordinating Center
International Breast Cancer Study Group (IBCSG)
Outcome results
None listed