Progressive or recurrent, locally advanced unresectable or metastatic HER2+ breast carcinoma in patients who have not received previous chemotherapy for the advanced disease.
Conditions
Interventions
Trade Name: Kadcyla
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: TRASTUZUMAB EMTANSINE
CAS Number: 1018448-65-1
Other descriptive name: TRASTUZUMAB EMTANSINE
Co
Sponsors
SOLTI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written Informed Consent for all study procedures in accordance with the local regulatory requirements prior to starting any Protocol specific procedures. 2.To provide tumor tissue or to have the possibility to collect newly tumor sample from the patient to be able to perform PAM50 analysis. The minimum conditions to achieve this are 1) presence of at least 1 tumor core with a minimum tissue area of 10mm2, 2) with at least 35% of tumoral cells and 3) enough tissue to perform at least 3 sections of 10 ?m each. 3.Women. 4.Age ? 18 years. 5.ECOG performance status of 0 or 1. 6.Invasive HER2+ breast cancer assessed centrally, defined by the clinical guidelines of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) (Wolff JCO 2013): a)IHC 3+ overexpression (circumferential membrane staining that is complete, intense, observed in >10% of the invasive tumor cells) b)In situ Hybridization positive (ISH: FISH/CISH/SISH >10% of the invasive tumor cells and by count of at least 20 cells in the area) based on: ?Single probe average HER2 gene copy number f ? 6 signals/cell ?Dual probe HER2/CEP17 ratio ? 2.0 with an average HER2 gene copy number ? 4.0 signals/cell ?Dual probe HER2/CEP17 ratio ? 2.0 with an average HER2 gene copy number 100,000/mm3 d)Serum creatinine ? 1.5x Upper limit of normal (ULN). e)Total bilirubin < 1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT and/or ALAT < 2.5 UNL, alkaline phosphatase < 5 UNL (unless bone metastases are present in the absence of any liver disorders). f)International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) <1.5 x ULN (except in cases of ongoing anticoagulant treatment). 10.Baseline left ventricular ejection fraction (LVEF) ? 50% measured by echocardiography (ECHO) or isotopic ventriculography (MUGA). 11.? HCG pregnancy test negative (serum) for premenopausal women of childbearing potential (biologically capable of having children) and for women who have been menopausal for fewer than 12 months. All patients biologically capable of bearing children must agree and commit to the use of a reliable contraceptive method from 2 weeks prior to the administration of the first dose of the investigational medicinal product until 28 7 months after the last dose of the study treatment. 12.Absence of psychological, family, sociological or geographical conditions that could potentially hinder compliance with the study Protocol and monitoring calendar. These conditions must be discussed w
Exclusion criteria
Exclusion criteria: 1.History of systemic anti cancer therapy for MBC or locally advanced breast cancer, with the exception of previous hormonal treatments. oThe hormonal regimen for MBC may not include HER2 targeted therapy. 2.Interval 30% of the bone marrow. 10.Symptomatic hypercalcemia requiring treatment with bisphosphonates in the 21 days prior to the first study treatment. Patients receiving treatment with bisphosphonates specifically for the prevention of skeletal events and who do not have a RECENTLY history of clinically significant hypercalcemia are eligible. 11.Current peripheral neuropathy, grade ?2 according to NCI CTCAE version 4.03. 12.Abnormal liver function defined as: o AST or ALT > 2.5 x ULN o AST or ALT > 1.5 x ULN with simultaneous serum alkaline phosphatase >2.5 x ULN. The serum alkaline phosphatase may be >2.5 x ULN only in the presence of bone metastases and AST (SGOT) and ALT (SGPT) 500 mg/m2 ?Liposomal doxorubicin > 500 mg/m2 ?Epirubicin > 720 mg/m2 ?Mitoxantrone > 120 mg/m2 ?Idarubicin > 90 mg/m2 ?If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 500 mg/m2 of doxorubicin. 14.Cardiopulmonary dysfunction defined as: o Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg) despite optimum medical treatment. o Serious cardiac arrhythmia or angina controlled inadequately, not controlled with adequate medication. o Inadequate LVEF at study start, defined as LVEF < 50% in any ECHO or MUGA. o History of symptomatic congestive heart failure (SCHF): Grade ? 2 according to NCI CTCAE version 4.03 criteria or class ? II according to the criteria of the New York Heart Association (NYHA). o History of decrease of the LVEF to < 40% or symptomatic CHF after prior treatment with trastuzumab. o Myocardial infarction in the 6 months prior to randomization. o Current resting dyspnea due to complications of the advanced malignant disease, or other diseases requiring continuous oxygen therapy. 15. Current uncontrolled serious systemic disease that is active (for example, clinically significant cardiovascular disease, pulm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the early efficacy (measured as the rate of PFS at 4 months) of T DM1 together with SI docetaxel versus monotherapy treatment with T DM1;Secondary Objective: 2.To compare the combination of T DM1 together with SI docetaxel versus monotherapy treatment with T DM1 in terms of: a.Overall Response Rate (ORR), measured as the percentage of patients who achieve Complete Response (CR) and/or Partial Response (PR), in accordance with the RECIST 1.1 criteria throughout the study treatment. b.Clinical Benefit Rate (CBR), measured as the percentage of patients with CR, PR or Stable Disease (SD) with a duration of at least 6 months. c.Duration of Response (DR) d.Overall Survival (OS) e. Progression Free Survival (PFS) f.Breast cancer specific survival, measured as the time from randomization to death due to breast cancer. 3. To compare the safety and tolerability of both treatment regimens. 4. To compare the cardiac safety of both treatment regimens. 5. To compare the hepatic safety of both treatment regimens.;Primary end point(s): To compare the early efficacy (measured as the rate of PFS at 4 months) of T DM1 together with SI docetaxel versus monotherapy treatment with T DM1, in patients recently diagnosed with progressive or recurrent, locally advanced or metastatic HER2+ breast cancer who have not received previous chemotherapy for the advanced disease.;Timepoint(s) of evaluation of this end point: 24 months after the First Patient In. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 2.To compare the combination of T DM1 together with SI docetaxel versus monotherapy treatment with T DM1 in terms of: a.Overall Response Rate (ORR), measured as the percentage of patients who achieve Complete Response (CR) and/or Partial Response (PR), in accordance with the RECIST 1.1 criteria throughout the study treatment. b.Clinical Benefit Rate (CBR), measured as the percentage of patients with CR, PR or Stable Disease (SD) with a duration of at least 6 months. c.Duration of Response (DR), measured as the time between achieving CR or PR until Disease Progression (DP). d.Overall Survival (OS), measured as the time from randomization to death from any cause. e.Progression Free Survival (PFS), measured as the time from randomization to progression or death from any cause. f.Breast cancer specific survival, measured as the time from randomization to death due to breast cancer. 3.To compare the safety and tolerability of both treatment regimens. 4.To compare the cardiac safety of both treatment regimens. 5.To compare the hepatic safety of both treatment regimens Exploratory objectives 6.To assess if the PAM50 intrinsic subtypes (HER2 enriched in comparison with the rest) predict benefit (in terms of ORR and PFS) based on the addition of docetaxel. 7.To assess if the PAM50 intrinsic subtypes (HER2 enriched in comparison with the rest) predict the clinical outcome, in terms of CR or PFS, regardless of the addition of docetaxel 8.To assess if Ki67 predict benefit (in terms of ORR and PFS) based on the addition of docetaxel.;Timepoint(s) of evaluation of this end point: At the end of the treatment | — |
Countries
Spain
Contacts
Public ContactOficina Operaciones
SOLTI
Outcome results
None listed