HER2 POSITIVE METASTATIC BREAST CANCER MedDRA version: 21.0 Level: LLT Classification code 10025541 Term: Malignant breast neoplasm System Organ Class: 100000004864
Conditions
Interventions
Trade Name: KADCYLA
Product Name: KADCYLA
Product Code: [Trastuzumab emtansine]
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: TRASTUZUMAB EMTANSINE
Current Spo
Sponsors
ISTITUTI FISIOTERAPICI OSPITALIERI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all the following inclusion criteria to be eligible for enrolment into the study: 1. Signed, written informed consent (approved by the institutional review board or independent ethics committee) obtained prior to any study specific procedure initiation or treatment as confirmation of the patient’s awareness and willingness to comply with the study requirements 2. Female aged >18 years at the time of the randomization 3. Histological or cytological confirmed and documented carcinoma of the breast with metastatic disease [confirmed by histology, cytology or other clinical means (e.g. CT, MRI)]. Subjects must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 4. Documentation of HER2 overexpression or gene amplification, in the invasive component of either the primary tumor or metastatic disease site as defined as: - 3+ by Immunohistochemistry (IHC Dako) and/or - HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of =2.0] 5. Patients must have been already treated with pertuzumab-trastuzumab and taxane in the metastatic setting 6. Allowed prior neoadjuvant/adjuvant treatment 7. Life expectancy of > 6 months as assessed by the treating investigator 8. Left ventricular ejection fraction (LVEF) =50% during a baseline period of 28 days, as determined by either echocardiography (ECHO) or multigated acquisition (MUGA) scan. ECHO is the preferred method; the same method of LVEF assessment, ECHO or MUGA, must be used throughout the study and, to the extent possible, be obtained at the same institution. Assessments made within 42 days prior to randomisation are not required to be repeated. 9. ECOG PS 0-2 10. Adequate haematological function as defined by: ANC ¿ 1.5 x 109/L, platelet count ¿100 x 109/L, haemoglobin ¿ 10 g/dL. 11. Adequate renal function, as defined by: creatinine¿ 1.5 x UNL 12. Adequate hepatobiliary function, as defined by the following baseline liver function tests: total serum bilirubin ¿1.5 upper normal limit (UNL); alanine aminotransferase (ALT), aspartate aminotransferase (AST) ¿ 2.5xUNL; alkaline phosphatase (AP) ¿ 2.5xUNL; if total alkaline phosphatase (AP) > 2.5xUNL, alkaline phosphatase liver fraction must be ¿ 2.5xUNL 13. All prior treatment related toxicities must be CTCAE (Version 4.03) = Grade 1 at the time of randomization 14. Adequate contraception for all fertile patients 15. Negative pregnancy test 16. Allowed previous and concomitant bisphosphonates/denosumab 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 71 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. History of persistent Grade = 2 hematologic toxicity resulting from previous systemic therapy 2. Current peripheral neuropathy of NCI-CTCAE, Version 4.03, Grade = 3 at randomization 3. History of other malignancy within the last 5 years, except for a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma 4. Patients not pretreated with pertuzumab as first-line regimen for metastatic disease 5. Patient treated with more than one regimens for metastatic disease 6. Serious cardiac illness or medical conditions including but not confined to: history of documented congestive heart failure (CHF) or systolic dysfunction (LVEF 180mm Hg or diastolic >100mm Hg) 7. Inadequate organ function, evidenced by the following laboratory results within 28 days prior to randomization: • Inadequate bone marrow function: Absolute neutrophil count upper limit of normal (ULN) (unless the patient has documented Gilbert’s syndrome);AST (SGOT) or ALT (SGPT) >1.5 times ULN with concurrent serum alkaline phosphatase >2.5 times ULN (unless bone metastases are present); • Inadequate renal function: Serum creatinine>2.0 mg/dL or >177 µmol/L; • International normalised ratio and activated partial thromboplastin time or partial thromboplastin time >1.5 times ULN (unless on therapeutic coagulation). 8. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures) 9. Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment 10. History of receiving any investigational treatment within 30 days of randomization or 5 half-lives, whichever is longer, preceding the first dose of study treatment 11. Known immediate or delayed hypersensitivity to any of the study drugs or idiosyncrasy to drugs chemically related to any of the study agents or their excipients that, in the opinion of the Investigator, contraindicates their participation 12. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol, or have a concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent) 13. Lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medications 14. Concurrent interventional or non-interventional studies 15. History of current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease pe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Our trial will primarily aim at evaluating the clinical activity of T-DM1 vs lapatinib/capecitabine in HER2+ ABC pertuzumab- pretreated pts. PFS, defined as the time elapsed between randomization and objective cancer progression or death, will be our primary endpoint for treatment efficacy. We will also report on 1. OS, defined as the time elapsed between randomization and death from any cause, and 2. Adverse events (AE).;Secondary Objective: Specific Aim 2: The secondary objective is to evaluate the predictive role of circulating miRNA and ctDNA in HER2+ ABC pts treated in second-line. Circulating biomarkers will be assessed at baseline, after 3 cycles of therapy and at treatment discontinuation from any cause. Specific Aim 3: This task aims at exploring the potential mechanisms of resistance to pertuzumab in pertuzumab-resistant CL. The most promising candidate biomarkers will be validated in bioptic samples from pts whose disease progressed after pertuzumab treatment.;Primary end point(s): PROGRESSION FREE SURVIVAL;Timepoint(s) of evaluation of this end point: 6 MONTHS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SAFETY (CTCAE V4); OVERALL SURVIVAL;Timepoint(s) of evaluation of this end point: EACH CYCLE; 12 MONTHS | — |
Countries
Italy
Contacts
Public ContactOncologia Medica 2
Istituti Fisioterapici Ospitalieri
Outcome results
None listed