Women with a diagnosis of invasive unilateral non metastatic HER2-positive and ER-positive breast cancer suitable for neoadjuvant therapy MedDRA version: 17.1 Level: LLT Classification code 10006283 Term: Breast neoplasm malignant female System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Herceptin
Product Name: Herceptin
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Current Sponsor code: N.A.
Sponsors
FONDAZIONE MICHELANGELO - AVANZAMENTO DELLO STUDIO E DELLA CURA DEI TUMORI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients aged 18 years or older with tumors suitable for neoadjuvant treatment 2. Early (> 1.5 cm) or locally advanced untreated breast cancer 3. Histologically confirmed invasive unilateral breast cancer 4. HER2-positive disease centrally confirmed 5. Positive estrogen receptor (ER) > 10% and known progesterone receptor (PgR) 6. Available paraffin-embedded tumor block taken at diagnostic biopsy for central retrospective confirmation of HER2 and ER eligibility and for assessment of Ki67 value and apoptosis is mandatory 7. All patients must agree to provide tumor tissues for centralized assessment of KI67 values and apoptosis at the required timelines (2 weeks from starting protocol therapy and at surgery) 8. ECOG performance status 0 or 1 9. Written informed consent to participate in the trial (approved by the Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures 10. Willing and able to comply with the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: 1. Evidence of bilateral invasive breast cancer or metastatic disease (M1) 2. Pregnant or lactating women. Documentation of a negative serum pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle 3. Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception, for example abstinence, an intra-uterine device, or double barrier method of contraception up to 7 months from the last dose of either anticancer study drug 4. Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy 5. Previous extensive radiotherapy 6. Previous investigational treatment for any condition within 4 weeks of registration date 7. Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol 8. Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results. Patients with curatively treated basal cell carcinoma of the skin, stage 1 uterine cancer or in situ cervix cancer are generally eligible. 9. Other serious illness or medical condition including: history of documented congestive cardiac failure; angina pectoris requiring anti-anginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias 10. Baseline left ventricular ejection fraction (LVEF) 480 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP) 12. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs 13. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus 14. Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors or inducers 15. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia) 16. Any of the following abnormal baseline hematological values: a. Absolute Neutrophil Count (ANC) 1.5 ? ULN (upper limit of normal) (except for patients with clearly documented Gilbert’s syndrome) b. Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.25 ? ULN c. Alkaline phosphatase > 2.5? ULN d. Serum creatinine > 1.5 ? ULN e. INR > 2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: . Characterize changes of Ki67 from baseline before therapy and at 2 weeks and at surgery (approximately 22 weeks after start of neoadjuvant therapy with HPPF). . Characterize changes in apoptosis from baseline before therapy and at surgery (approximately 22 weeks after start of neoadjuvant therapy with HPPF). . Study the tolerability profile of the combination;Secondary Objective: . Assess the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery . Define the clinical objective response rate at the end of the combination . Conduct molecular and clinical analyses to assess the presence of informative markers of benefit in addition to Ki67 and apoptosis;Primary end point(s): • Changes from baseline in KI67 score • Changes from baseline in apoptosis score ;Timepoint(s) of evaluation of this end point: Primary end point will be evaluated, for each patient, 6 months after the registration date. Considering an enrollment period of 12 months, the primary end point will be evaluated 20 months after the first patient enrolled. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Assess the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery • Define the clinical objective response rate at the end of the combination • Conduct molecular and clinical analyses to assess the presence of informative markers of benefit in addition to Ki67 and apoptosis ;Timepoint(s) of evaluation of this end point: Considering an enrollment period of 12 months, the secondary end point will be evaluated 20 months after the first patient enrolled. | — |
Countries
Italy
Contacts
Public ContactClinical Operation
Michelangelo Tech S.r.l
Outcome results
None listed